Premalignant lesions of the colorectum.
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A case of bilateral juvenile polyps and unilateral adenocarcinoma at the ureterocolic junctions occurring 40 years after ureterosigmoidostomy for exstrophy of the bladder is reported. Although adenocarcinoma of colon at the anastomotic site represents an uncommon late complication of ureterosigmoidostomy, patients undergoing this form of urinary diversion have a risk of developing colonic carcinoma that is 100 to 550 times greater than the normal population. Moreover this complication is being reported with increasing frequency in the literature. Different pathogenetic factors may play a role in carcinogenesis, but none has been satisfactorily proven. We suggest the possibility that polyps developing at the site of a ureterocolic junction may represent precancerous lesions.
Screening colonoscopy aims at a reduction of colorectal cancer mortality. The efficacy is undetermined due to lack of controlled trials. However, screening colonoscopy is generally accepted in asymptomatic patient with a considerably increased risk for carcinoma in particular in case of familial adenomatous polyposis coli, hereditary nonpolypous colorectal cancer syndrome and adenomas detected by sigmoidoscopy. A positive cost/benefit ratio can also be expected in first-degree relatives of patients with familial sporadic colorectal carcinoma. To date the efficacy of colonoscopic surveillance of patients with extensive ulcerative colitis remains undetermined in spite of an increased risk of cancer in the long-term course. In people with an average risk for colorectal cancer the probability of a development of carcinoma might be reduced by about 45% by once-only sigmoidoscopy performed at the age of 50-60 years. Further reduction can theoretically be expected from routine colonoscopy. However, before a general recommendation can be given, the efficacy must be proved in a randomised controlled trial.
OBJECTIVES: We attempted to determine an accurate frequency of new polyp growth in a cohort of veteran male patients who were initially cleared of polyps by tandem colonoscopy. METHODS: Followup colonoscopy was performed 2 yr after tandem colonoscopy. A polyp was categorized as "new" if it was not located in a segment of the colon or rectum that had harbored a neoplastic polyp of the same histology at tandem colonoscopy, in contradistinction to lesions designated as "same-segment" polyps. RESULTS: Fifty-eight of 90 patients who had tandem colonoscopy as a part of a previous study were available for follow-up colonoscopy for 2 yr. Ninety-one percent had a history of benign neoplastic polyps or cancer. Neoplastic polyps were documented in 52% (95% CI, 45-74%) of patients at followup, and 38% (95% CI, 26-52%) were found to have a total of 31 "new" lesions. All new lesions were tubular adenomas. The largest number of new polyps in an individual patient was four, and the largest new lesion was 20 mm in size with a flat, linear configuration. Most (25/31) new polyps were < or = 5 mm, and the number of neoplastic polyps per patient at follow-up was less than at tandem colonoscopy. CONCLUSIONS: Approximately one-half of older, male patients with a history of neoplastic polyps will demonstrate neoplastic polyps at 2 yr. In at least one-third of patients, these appear to be new lesions. In some patients, de novo neoplastic polyps can grow to > or = 1 cm within 2 yr.
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BACKGROUND: The cancerogenic process of colorectal cancer depends on a series of events involving oncogenes and inactivation of suppressor genes. This study concerns changes in DNA content, p53 and PCNA expression in human colon in dysplastic, precancerous and cancerous tissues. MATERIALS AND METHODS: These characteristics were analyzed in a series of hyperplastic polyps (HP), adenomas (AD), adenocarcinomas evolved within adenomas (AC-AD) and adenocarcinomas (AC) of the large bowel. DNA ploidy was analyzed by flow cytometry and PCNA and p53 expression was evaluated by immunohistochemistry using monoclonal antibodies PC10 and PAb 1801. RESULTS: Aneuploidy was found in 43/67 (64%) of AC and only occasionally in other subgroups (AC vs all other groups: 64% vs 99%; p = 0.00002). PCNA positivity gradually increased in the sequence from HP to AC and were significantly higher in AC compared to HP (90% vs 44%; p = 0.00007). p53 positive cells were found in 67% of AC while only occasionally in other groups (HP vs AC: p = 0.0002, AD (low dysplasia) vs AC: p = 0.001; AD (moderate dysplasia) vs AC: p = 0.001). CONCLUSIONS: These results demonstrated a progressive immunoreactivity for PCNA in the HP to AC sequence, while p53 positivity and aneuploidy seemed specific for colon carcinoma.
The results obtained in a series of 75 patients suffering from advanced cancer of the colon-rectum are examined. Survival of these patients is looked at as a function of the extent of surgical demolition, and as a function of postoperative chemotherapy. Demolition interventions were followed by much higher survival than was observed following palliative operations. At the same time, survival was higher in patients who underwent post-operative chemotherapy. The results therefore justify a more aggressive approach in advanced cancer of the colon-rectum.
Part I of this study [Spratt JS, Meyer JS, Spratt JA: J Surg Oncol 60:137-146, 1995] reviewed the early reports of investigators, predominantly mathematical biologists and statisticians considering the mathematical laws that would describe the growth of a neoplasm. Included were cytokinetic measurements of the mitotic index, thymidine labeling index, bromodeoxy-uridine labeling index, and the relation of these indices to the potential tumor volume doubling time. The actual doubling time of benign and malignant colonic neoplasms were reported. This second part provides the cumulative observations on the actual doubling times of pulmonary metastases, primary pulmonary cancers, skeletal sarcomas, melanomas, a chemodectoma, tumors of maxillary antrum, testicular cancers, prostate cancer, and the relation between the accumulation of multiple primary cancers and growth rates. The most complete data set is for breast cancer concluding that the cancer growth curve is a decelerating curve with great natural variance. Understanding of the rates of growth of human cancers is essential for understanding the spectrum of cancer behavior observed clinically.
Acromegalic patients have an increased prevalence of colonic neoplasms and lower peroxisome proliferator-activated receptor gamma (PPARgamma) levels, the latter acting as a tumor suppressor gene. In this study we evaluated the expression of PPARgamma in the biopsy samples of the polyps and outside polyps colonic mucosa from seven patients with active, untreated acromegaly, 11 with cured disease, and 15 controls. Serum GH and IGF-I levels were higher in patients with untreated acromegaly than in those with acromegaly in remission or controls (P = 0.003 and P = 0.002, respectively) The expression of PPARgamma mRNA (mean +/- SE) was 1) mucosa outside polyps, 24,188 +/- 3,254 transcripts in the controls, 22,432 +/- 2,006 transcripts in acromegaly in remission, and 1,952 +/- 342 transcripts in untreated acromegaly (P < 0.0001 vs. controls and acromegaly in remission); and 2) polyps mucosa, 1,554 +/- 236 transcripts in the controls, 1,112 +/- 143 in acromegaly in remission, and 1,570 +/- 251 in untreated acromegaly (P = NS among polyps groups and mucosa outside polyps of untreated acromegaly; P < 0.0001 vs. mucosa outside polyps of controls and acromegaly in remission). Eighty-five percent of the cells in the mucosa outside polyps from controls or acromegaly in remission were positive at immunohistochemistry, at variance with 45% of the cells from polyps mucosa from each group and from those of mucosa outside polyps of untreated acromegaly (P = 0.0002). In conclusion, patients with untreated acromegaly have reduced expression of PPARgamma in the mucosa outside polyps, which might be reversed by curing the disease; conversely, patients with acromegaly in remission have the same low levels of expression of PPARgamma in the polyps mucosa as untreated acromegaly or controls, supporting the concept that reduced expression of PPARgamma might be an early event in colonic tumorigenesis.
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A human colon carcinoma cell line was established from a metastatic lymph node of a patient with hereditary adenomatosis of the colon and rectum (ACR). Cells of this line, designated KMS-4, have been continuously propagated in culture during the past 24 months. The cells growing on the surface of culture dishes showed epithelial features, and, when inoculated into athymic nude mice, produced adenocarcinomas with a morphology similar to that of the original tumor. Electron micrographs showed that the cultured cells have desmosomes and numerous surface microvilli typical of colon epithelium. Chromosomal analysis revealed the cell line to be of human origin with a diploid mode of chromosome number, but the karyotypes examined were all abnormal. Most of the metaphases commonly had such abnormalities as 7p+, 12p+, +13, +16 and 17p+, accompanied by loss of chromosome No. 19 and/or 20, and, interestingly, all the metaphases contained 7p+ and +13. The cells had a log phase doubling time of 48 to 72 h. The cloning efficiency of the cells was 0.06% in the soft agar medium. Neither 12-O-tetradecanoylphorbol-13-acetate nor bile acids enhanced cell proliferation. The cells abundantly secreted CEA protein into the culture medium (700 ng/ml/106 cells during a 48 h period). The present colon carcinoma cell line derived from a genetically defined individual with ACR should prove useful for research in human oncology or genetics.
The records of all patients with familial polyposis coli and ulcerative colitis operated at The Mount Sinai Hospital were reviewed to determine the proportion of patients with cancer at the time of colon resection. Sixty-nine patients with familial polyposis coli undergoing operation between 1947 and 1983 were identified and 25 (36 percent) were found to have cancer. In the group with ulcerative colitis, 548 patients had surgical treatment between 1957 and 1983 and 65 (12 percent) had colonic cancer. There was a significant decrease in the proportion of patients with familial polyposis coli having cancer at the time of colon resection from 50 percent before 1968 to 20 percent since 1978. This change in cancer incidence was found to correlate with a decrease in the mean age at operation from 40 to 25 years. In the group with ulcerative colitis, the mean age at operation has remained essentially unchanged at 36 years. The proportion of patients with ulcerative colitis having cancer at the time of colon resection has remained constant throughout this study. Progression to carcinoma is still a significant concern in both familial polyposis coli and ulcerative colitis. Although removal of the colon and rectum prevents cancer development, patient selection and timing of the operation remain a difficult problem.
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The case of a signet ring cell carcinoma of the colon arising in an adenoma at the site of ureterosigmoidostomy after conversion to an ileal conduit is reported. Urine exposure to the colonic mucosa was present only for a short period before development of an adenoma with subsequent signet ring cell carcinoma transformation more than 15 years later. In the face of recent reports on adenocarcinoma in cases of bladder substitution or augmentation without any possible promoting influence of the fecal stream, the well known risk of neoplasia after sigmoidostomy remains unclear in its etiology.
Serrated adenoma is a recently described entity characterized by the presence of a hyperplastic (serrated) growth pattern combined with cytologic features of dysplasia. In contrast to conventional (nonserrated) adenomas, the molecular features of serrated adenomas have been poorly studied. Thus, it remains unclear if serrated adenomas are simply a morphologic variant of conventional adenomas or represent a different biologic entity. In this study, 46 serrated adenomas from 39 patients, 32 conventional (nonserrated) adenomas from 31 patients, and 18 hyperplastic polyps from 16 patients were evaluated for loss of heterozygosity (LOH) of APC, p53, p16, and 3p and for K-ras mutations of codons 12, 13, and 61 by polymerase chain reaction (PCR) analysis. Serrated adenomas demonstrated LOH of at least one genetic locus in 32.6% of cases. LOH of the APC gene, 3p, p53, and p16 was seen in 19.4%, 14.2%, 9.3%, and 13.8% of cases, respectively. K-ras mutations were observed in 18% of cases. Similar to serrated adenomas, conventional adenomas demonstrated at least one LOH event in 37.5% of cases and K-ras mutations in another 19% of cases. LOH of APC, 3p, p53, and p16 was observed in 22%, 33%, 5.8%, and 13.4% of cases, respectively. There were no significant differences in either the total number of genetic events or the presence of LOH of any of the individual markers between serrated adenomas and conventional adenomas. However, hyperplastic polyps showed LOH in 22% of cases and a single K-ras mutation (11%). The prevalence of LOH in hyperplastic polyps was lower than both serrated adenomas and conventional adenomas (P < .05). These results support the hypothesis that serrated adenomas represent a biologically similar morphologic variant of conventional adenomas.
Over a period of six years a total of 407 patients with polyps of the gastrointestinal tract were examined by gastroscopy and coloscopy and the findings analysed retrospectively. Among patients with colon polyps 10.5% were found also to have polypoid gastric lesions, among those with adenoma of the colon the prevalence was 11.7%. Only 2.4% of simultaneously diagnosed gastric lesions were found to be malignant or premalignant, a figure similar to the population average. But in patients with more than ten polyps of the colon both the prevalence of polypoid gastric changes and the significance of polyps with respect to precancerous lesions were clearly increased. On the other hand, in patients with epithelial polyps and/or glandular cysts colon polyps were found in 45%, in 42% with precancerous changes (adenoma). Thus patients with epithelial gastric polyps and glandular cysts probably constitute a group with a real additional risk of colon carcinoma. Regular coloscopy will thus reveal precancerous changes (adenoma) in the colon of 42% of such patients; coloscopic polypectomy will be an effective prophylactic measure against carcinoma of the colon.