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Colorectal polyp counts and cancer risk in familial adenomatous polyposis.

BACKGROUND & AIMS: In familial adenomatous polyposis, colorectal cancer prevention is by prophylactic colectomy, but dietary or chemopreventative strategies have been recently proposed in low-risk individuals. The aim of this study was to define predictive risk factors for colorectal cancer in familial adenomatous polyposis. METHODS: Between 1918 and 1993, 317 patients underwent colectomy. A multivariate analysis was performed to assess the relationship between colorectal cancer risk and polyp count, sex, and age at colectomy. RESULTS: The median polyp count was 842 (range, 78-7500), and cancer was found in 22% of patients. Polyp count and age, but not sex, predicted cancer risk. Patients with >1000 polyps had 2.3 times greater risk of cancer than those with <1000 polyps (P=0.006). Synchronous cancers increased with poly count (P<0.05). Each 10-year age group had a 2.4-fold difference in cancer risk (95% confidence interval, 1.9-3.2; P<0.001). Four cases of cancer occurred in patients at low risk (younger than 30 years of age, <1000 polyps; 3.3%). CONCLUSIONS: More adenomas and older age are associated with a higher risk of colorectal cancer. However, cancer does occur in low-risk individuals and may be missed by surveillance, making alternatives to prophylactic surgery inadvisable.

Adenomatous Polyposis Coli↗

Sporadic adenomatous polyp regression with exisulind is effective but toxic: a randomised, double blind, placebo controlled, dose-response study.

BACKGROUND AND AIMS: A 12 month, multicentre, randomised, double blind, placebo controlled, phase 3, dose-response study was carried out. Exisulind inhibits tumour growth by induction of apoptosis. The aim of our study was to investigate if exisulind induces regression of sporadic colonic adenomas. PATIENTS AND METHODS: A 12 month multicentre randomised double blind placebo controlled phase 3 dose response study was carried out. At baseline colonoscopy, left sided polyps (3-10 mm) were tattooed, measured, and left in place. Subjects received exisulind 200 or 400 mg, or placebo daily. Follow up sigmoidoscopy was performed after six months, and removal of any remaining polyps at the 12 month colonoscopy. The primary efficacy variable was change in polyp size from baseline. RESULTS: A total of 281 patients were enrolled and randomised; 155 (55%) fulfilled the criteria for the intention to treat (ITT) analysis and 114 (41%) fulfilled the criteria for the efficacy evaluation analysis (patients who underwent the 12 month colonoscopy). The decrease in median polyp size was significantly greater (p=0.03) in patients who received exisulind 400 mg (-10 mm2) compared with those who received placebo (-4 mm2). Complete or partial response was significantly higher in the exisulind 400 mg group (54.6%) compared with the placebo group (30.2%), and disease progression was significantly lower (6.1% v 27.9%) (p=0.04 and 0.02, respectively). Increased liver enzymes (8.4%) and abdominal pain (14.7%) were also reported at a greater frequency in the exisulind 400 mg group. CONCLUSION: Exisulind caused significant regression of sporadic adenomatous polyps but was associated with more toxicity. This model of polyp regression, short in its term and involving a comparatively small patient sample size, may be the best available tool to assess a therapeutic regimen before launching into large preventive clinical studies.

Adenomatous Polyposis Coli↗

Peutz-Jeghers polyps, dysplasia, and K-ras codon 12 mutations.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant, polyposis syndrome, associated with an increased risk of gastrointestinal and extragastrointestinal malignancy. Occasionally dysplasia occurs in PJS polyps. AIMS: In colorectal carcinomas, mutations in codon 12 of the K-ras oncogene are common and are found at similar frequency in precursor adenomas. Therefore, K-ras codon 12 point mutations in PJS polyps, were evaluated. MATERIALS AND METHODS: Fifty two PJS polyps, including four with dysplasia, collected from 19 patients with PJS, were analysed for mutations in the K-ras codon 12 by a mutant enriched polymerase chain reaction procedure, followed by allele specific oligodeoxynucleotide hybridisation. RESULTS: A K-ras codon 12 mutation was identified, in one colonic polyp with dysplasia. The mutation was found in the non-neoplasmic epithelial cells and not in the dysplastic component of the polyp. CONCLUSIONS: K-ras codon 12 point mutations are very rare in PJS polyps, by contrast with colorectal adenomas. The findings support previous evidence that there seems to be no intrinsic relation between K-ras codon 12 mutation and dysplasia.

Autoradiography↗

Familial polyposis coli: heterogeneous polyp expression in 2 kindreds.

We describe 2 extended kindreds supposedly manifesting familial multiple adenomatous polyposis coli (FPC), but which show marked heterogeneity in the phenotypic expression of colorectal adenomatous polyps. In one family, 2 individuals had diffuse polyposis at very early ages (7 and 10 years), while 6 others (aged 23 to 72 years) had solitary polyps only. Of the patients with solitary polyps, 2 had associated colonic malignancies (ages 26 and 35), while another had a prophylactic colectomy performed at age 46. In the second family, 5 of the 11 patients with evidence of polyps showed the classical presentation of FPC, while the remainder showed marked phenotypic variation. The marked variability in frequency and location of colon polyps points to the need to reassess our traditional criteria for diagnosis of FPC. The high risk of early onset colon cancer in patients from these families who have the most minimal manifestation, namely isolated polyps, recommends more careful scrutiny of supposedly unaffected members of all FPC kindreds.

Adult↗

Uroguanylin treatment suppresses polyp formation in the Apc(Min/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP.

The enteric peptides, guanylin and uroguanylin, are local regulators of intestinal secretion by activation of receptor-guanylate cyclase (R-GC) signaling molecules that produce cyclic GMP (cGMP) and stimulate the cystic fibrosis transmembrane conductance regulator-dependent secretion of Cl- and HCO3-. Our experiments demonstrate that mRNA transcripts for guanylin and uroguanylin are markedly reduced in colon polyps and adenocarcinomas. In contrast, a specific uroguanylin-R-GC, R-GCC, is expressed in polyps and adenocarcinomas at levels comparable with normal colon mucosa. Activation of R-GCC by uroguanylin in vitro inhibits the proliferation of T84 colon cells and elicits profound apoptosis in human colon cancer cells, T84. Therefore, down-regulation of gene expression and loss of the peptides may interfere with renewal and/or removal of the epithelial cells resulting in the formation of polyps, which can progress to malignant cancers of the colon and rectum. Oral replacement therapy with human uroguanylin was used to evaluate its effects on the formation of intestinal polyps in the Min/+ mouse model for colorectal cancer. Uroguanylin significantly reduces the number of polyps found in the intestine of Min/+ mice by approximately 50% of control. Our findings suggest that uroguanylin and guanylin regulate the turnover of epithelial cells within the intestinal mucosa via activation of a cGMP signaling mechanism that elicits apoptosis of target enterocytes. The intestinal R-GC signaling molecules for guanylin regulatory peptides are promising targets for prevention and/or therapeutic treatment of intestinal polyps and cancers by oral administration of human uroguanylin.

Adenocarcinoma↗

Solitary Peutz-Jeghers type polyp of the duodenum containing a focus of adenocarcinoma.

The case of an 84-year-old woman with evidence of continuous gastrointestinal bleeding is presented. A barium study and endoscopy showed a 25 x 20 mm sized semipedunculated polyp in the second portion of the duodenum. No other lesion was found throughout the entire gastrointestinal tract, and endoscopic resection of the duodenal polyp was performed. The resected polyp showed typical histologic features of a Peutz-Jeghers type hamartomatous polyp, although the patient lacked any familial history and signs related to the Peutz-Jeghers syndrome. A focus of adenocarcinoma was also found within the polyp. The present case would appear to be the first demonstration of a solitary Peutz-Jeghers type hamartomatous polyp of the duodenum containing a focus of adenocarcinoma.

Adenocarcinoma↗

Detection of proximal adenomatous polyps with screening sigmoidoscopy: a systematic review and meta-analysis of screening colonoscopy.

BACKGROUND: The relative effectiveness of flexible sigmoidoscopy compared with colonoscopy to screen for colorectal cancer depends on the magnitude of the association between findings in the proximal and distal colon and the false-negative rate of screening sigmoidoscopy for proximal neoplasia. To address this, we performed a systematic review and meta-analysis of screening colonoscopy studies. METHODS: Published studies through July 31, 2000, of asymptomatic patients undergoing screening colonoscopy were identified from the MEDLINE database. We generated pooled estimates of the odds ratio for the association between findings in the distal and proximal colon and the prevalence of isolated proximal adenomatous neoplasia. RESULTS: Using the sigmoid-descending colon junction to identify the beginning of the distal colon, the pooled odds ratio for the association between distal adenomatous polyps and any proximal neoplasia was 2.40 (95% confidence interval [CI], 1.42-4.05). Diminutive distal adenomatous polyps were also associated with proximal neoplasia (odds ratio, 2.36; 95% CI, 1.30-4.29). Distal hyperplastic polyps were not associated with proximal neoplasia (odds ratio, 1.44; 95% CI, 0.79-2.62). The prevalence of isolated advanced proximal neoplasia in the 3 studies was 2%, 3%, and 5%. Using the sigmoid-descending colon junction to identify the beginning of the distal colon yields a pooled estimate of isolated proximal neoplasia of 16.3% (95% CI, 13.6%-19.1%). CONCLUSIONS: Distal adenomatous polyps, including diminutive distal adenomatous polyps, are associated with an increased prevalence of synchronous proximal neoplasia. Two percent to 5% of patients undergoing screening colonoscopy may have isolated advanced proximal neoplasia. Even more patients may have isolated nonadvanced proximal neoplasia.

Adenomatous Polyps↗

Relationship between breast cancer and colorectal adenomatous polyps. A case-control study.

Although there is a known reciprocal association between breast and colorectal cancer in women, few studies have investigated whether a similar association exists between breast cancer and colorectal adenomatous polyps, known to be precursor lesions for colon cancer. A case-control study was conducted on patients in three colonoscopy practices in New York to determine possible risk factors for adenomatous polyps. Among women studied, there were 128 patients with incident adenomatous polyps and 284 control subjects who underwent colonoscopy and had no colorectal neoplasia. No significant association between the incidence of an adenomatous polyp in the colon or rectum and a history of breast cancer was found (odds ratio, 0.71; 95% confidence interval, 0.34 to 1.64). If shared risk factors for breast and colorectal cancer are the reasons for the concurrence of these two malignant lesions, these results suggest that these factors act at the level of promoting adenomatous polyps of the colon and rectum into colorectal cancer.

Adult↗

Multiple polyps of esophagus, stomach, colon, and rectum accompanying rectal cancer in a patient with constitutional chromosomal inversion.

BACKGROUND: It has been reported that colorectal carcinomas are caused by a multistage process. In patients with familial adenomatous polyposis, carcinoma of the colorectum frequently develops and occasionally polyps develop in the upper gastrointestinal tract. Chromosomal deletion often is found for chromosomes 5, 17, and 18, on which tumor suppressor genes are located. Furthermore, loss of the alleles of loci on chromosome 3 has been reported in renal cell carcinoma, small cell lung carcinoma, and mixed salivary gland tumor in hereditary and sporadic cases. These data support the concept of a recessive mechanism for the development of human tumors. PATIENTS AND RESULTS: The authors report the case of a 48-year-old woman with rectal cancer accompanied by multiple polyps in the esophagus, stomach, and colorectum. Histologically, the polypoid lesions in the esophagus, stomach, and colorectum showed a thickened mucosa, hyperplastic polyps, and mixed hyperplastic adenomatous polyps, respectively. Karyotype analysis showed 46, xx, inv(3)(p12.2q25.3) in all 20 inspected peripheral lymphocytes. By Southern blot with a c-raf probe, one allele of the c-raf-1 gene, which has been mapped on chromosome 3p25, was deleted from the rearranged chromosome 3 in the peripheral lymphocytes, intact colonic mucosa, and cancer tissue. CONCLUSIONS: These results suggest that the development of hyperplastic polyps and carcinoma of the rectum results from the allelic loss in chromosome 3p, as has been reported for solid tumors at other sites.

Chromosome Aberrations↗

Prevalence of colorectal polyps in Filipinos. An autopsy study.

From May 1988 to May 1990, a prospective autopsy study was performed in patients who died at the Philippine General Hospital in Manila, Philippines. Patients younger than 10 years of age, patients with a history of large bowel resection, and patients whose deaths were related to trauma were excluded. There were 416 patients; 246 were males, and 170 were females. The mean age was 47 years (range, 11-95 years). Six of the 416 patients (1.4 percent) were found to have polyps. One patient had an inflammatory polyp, one was diagnosed with familial adenomatous polyposis, and one had an associated cecal carcinoma. Five "sporadic" adenomatous polyps were found in the remaining three patients (prevalence rate, 0.7 percent). All of the adenomatous polyps were located distal to the hepatic flexure and exhibited only mild atypia. The mean size was 6.4 mm (range, 2-20 mm). The incidence of colorectal adenomas in Filipinos is low compared with that in age-adjusted Western populations. This finding coincides with a low incidence of colorectal carcinoma. The documentation of a low risk for adenomatous polyps and colorectal cancer indicates that it would be difficult for massive screening programs to demonstrate a significant positive impact on the early detection of colorectal neoplasias in the Filipino general population.

Adolescent↗

Antrochoanal polyps in children: CT findings and differential diagnosis.

Antrochoanal polyp (Killian polyp) is an infrequent, usually solitary, benign, slowly growing lesion that arises from the maxillary antrum and reaches the choana. These polyps have a discrete male predominance and are diagnosed usually between the third and the fifth decades of life. This report is based on three cases of antrochoanal polyp, occurring in the pediatric group, and the objective is to demonstrate their different CT characteristics, principal differential diagnoses, and potential complications. We emphasize that in all three cases of our series the growth of the polyp to the choana is through the accessory ostium.

Adolescent↗

Endoscopic mucosal resection of large sessile colorectal polyps with submucosal injection of hypertonic 50 percent dextrose-epinephrine solution.

PURPOSE: Before endoscopic mucosal resection of large sessile colorectal polyps, injection of solution into submucosa cushions and isolates the tumor, although there is little information as to which solution with optimal effect should be used. This study investigated the effectiveness of endoscopic mucosal resection by use of a hypertonic dextrose plus epinephrine solution for large sessile colorectal polyps. METHODS: We removed 59 large sessile colorectal polyps in 59 patients by introducing an endoscopic submucosal hypertonic dextrose plus epinephrine injection technique. Endoscopic evaluations were repeated at 3, 6, and 12 months or longer. If no residual tumor was observed endoscopically and histologically at one year or more, the patient was considered to be "cured." The main outcome measurements were the mean amount of solution injected, mean disappearance time of solution, safety, complications, and recurrence at follow-up. RESULTS: Of the 59 large sessile colorectal polyps, 23 (39 percent) were resected en bloc and 36 (61 percent) piecemeal. The mean amount of hypertonic dextrose plus epinephrine solution injected was 24.42 +/- 17.52 ml, and its mean disappearance time was 13.61 +/- 5.21 (range, 7-21) minutes. Of the 36 patients treated with piecemeal resection, 18 (50 percent) required additional endoscopic interventions. In patients who entered the follow-up surveillance protocol for one year or longer, the cure rate by en bloc resection was 100 percent (23/23) and that by piecemeal intervention was 96.78 percent (30/31). Four patients (6.8 percent) had local bleeding after endoscopic mucosal resection that was mainly controlled endoscopically. CONCLUSIONS: Endoscopic mucosal resection after submucosal hypertonic dextrose plus epinephrine solution injection, with an intensive follow-up program, seems to be a safe and effective treatment for large sessile colorectal polyps.

Aged↗

Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel.

A monoclonal antibody to bromodeoxyuridine was used in tissue specimens previously incubated with bromodeoxyuridine to show S-phase cells by immunohistochemical technique. Biopsy specimens of normal mucosa (n = 10), hyperplastic polyps (n = 10), adenomas with low-grade dysplasia (n = 20), adenomas with high-grade dysplasia (n = 10), and invasive adenocarcinomas (n = 10) of the large bowel were studied. Labeling index and cell proliferative patterns were analyzed. No statistically significant difference was found in labeling index between normal mucosa and hyperplastic polyps or between adenomas with high-grade dysplasia and adenocarcinomas. The labeling index was significantly lower in normal mucosa and in hyperplastic polyps than in adenomas and adenocarcinomas (p less than 0.001). The difference in labeling index between adenomas with high-grade dysplasia and low-grade dysplasia was also statistically significant (0.01 less than p less than 0.05). In normal mucosa and in hyperplastic polyps the proliferative zone was confined to the lower two-thirds of the crypt; no kinetic activity was found in the upper portions of the crypt or in surface epithelium. In adenomas the labeled cells were either present in the upper third or scattered along the whole axis of the crypt and in the surface epithelium. Labeling patterns in invasive carcinomas were similar to those observed in adenomas with high-grade dysplasia. The difference in proliferative patterns between hyperplastic polyps and adenomas supports a different significance of the two polypoid lesions in the histogenesis of large bowel cancer; our results confirm the subsequent steps of the adenoma-carcinoma sequence. Immunohistochemical labeling patterns observed with monoclonal antibody to bromodeoxyuridine in polypoid and cancer lesions of the large bowel are similar to those described by autoradiographic studies.

Adenocarcinoma↗

Endoscopic resection of large sessile colorectal polyps.

Colonoscopic removal of large, sessile polyps is difficult, but can be successfully carried out by experienced endoscopists. "Piecemeal" resection with an electrocautery snare was performed at our institution in 108 patients with 132 such lesions. The mean size of the unresected polyps was 3.0 cm. Complications occurred in 3.0% of polypectomies (3.8% of patients), with bleeding necessitating transfusion in 2.3% of polypectomies (2.8% of patients), and microperforation (probable) in the remainder. No patient required emergency surgery due to a complication. In 65 patients (60%), colonoscopic resection and follow-up alone was carried out. Of these, adenomas recurred/persisted in 28%, most of which were successfully re-resected. Nearly half of all recurrent polyps occurred after at least one negative intervening examination. Carcinoma later appeared in 17% of the recurrences despite apparent initial complete resection of a previously benign polyp. Cure was ultimately achieved in 88% of endoscopically managed patients. Surgical resection was required in 27% of patients, mostly following the initial polypectomy when invasive carcinoma was found in the specimen. No residual tumor was later found in 41% of the colon specimens from these patients. Ninety-one percent of cancers were favorable stage, whether discovered early or late. Follow-up colonoscopy was achieved in 77% of patients over an average of 3.7 years. Metachronous polyps were excised in 52 patients (63%) and metachronous carcinoma was diagnosed in 3 patients (3.6%). An aggressive regimen of surveillance colonoscopy is warranted in these patients to detect and manage local recurrences and to remove subsequent adenomas. Endoscopic resection of large sessile adenomas can be safe and effective.

Aged↗

Colorectal polyps and cancers diagnosed by pathologists in Ile de France Region. Crisapif-Petri Study.

OBJECTIVES: The aim of this study was to evaluate the histological characteristics of adenomatous polyps (AP), non adenomatous polyps (NAP), and colorectal cancers (CRC) diagnosed in the greater Paris area. MATERIAL AND METHODS: Pathologists filled out an identification and histological questionnaire for each biopsy or surgical specimen received between 20/09/02 and 20/12/02, which had at least one colorectal polyp or CRC, taken from a patient of the greater Paris area. RESULTS: The participation rate of pathologists was 73.3% and 10,396 patients with 16,681 lesions were included. Lesions consisted in 1,223 CRC among 1,107 patients, 9,280 AP and 6,178 NAP. Mean age of patients with CRC was 68 years, with at least one AP without CRC 62 years, and with at least one NAP without CRC or AP 58 years. The mean number of polyps per patient was 1.4, and increased with age. Average size of AP was larger than that of NAP and the size increased with age for AP but not NAP. pTNM staging of CRC was: pT0, 1% pT1, 4% pT2, 13% pT3, 63% pT4, 19% N0, 55% N1, 24% N2, 19% Nx, 2%. CONCLUSION: This study provides detailed data on colorectal polyps and colorectal cancers in the greater Paris region, which does not have a cancer registry. Repeated surveys could be helpful for evaluating the efficacy of screening programs in the general population.

Adenomatous Polyps↗

Bowel movement, use of laxatives and risk of colorectal adenomatous polyps among women (United States).

BACKGROUND: Infrequent bowel movements and use of laxatives have been hypothesized to increase risk of colorectal neoplasia. However, the few existing epidemiologic studies in humans have been inconclusive. PURPOSE: To investigate prospectively the associations of bowel movement frequency and laxative use with the occurrence of adenomatous colorectal polyps in women. METHODS: A total of 17,400 women 36-61 years of age, without previous diagnosis of cancer or polyps, responded to a mailed questionnaire in 1982 that assessed bowel movement frequency and use of laxatives and had an endoscopy between 1984 and 1996. Between 1984 and 1996, 906 cases of adenomatous polyps (496 classified as small (< 1 cm), 358 classified as large (> or = 1 cm) and 52 unclassified) were documented. Relative risks (RRs) of adenomas and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: After controlling for adenoma risk factors, the multivariate RRs associated with having bowel movements every third day or less compared to once daily were 0.9 (95% CI: 0.7-1.2) for total colorectal adenomas, 1.0 (95% CI: 0.7-1.5) for large adenomas and 1.0 (95% CI: 0.7-1.3) for adenomas of the colon only. The multivariate RRs associated with weekly to daily laxative use compared to never use were 0.9 (95% CI: 0.7-1.1) for total colorectal adenomatous polyps, 1.0 (95% CI: 0.7-1.5) for large adenomas and 0.8 (95% CI: 0.6-1.2) for colon adenomatous polyps only. CONCLUSION: These findings do not support an association between infrequent bowel movement or laxative use and risk of colorectal adenomas.

Adenomatous Polyps↗

Virtual colonoscopy for the detection of colorectal polyps and cancers in a Chinese population.

AIM: The aim of this study is to assess the sensitivity of virtual colonoscopy in detecting colorectal polyps and cancers in a Chinese population. METHODS: Seventy-one consecutive Chinese patients (38 men and 33 women) referred for diagnostic colonoscopy were recruited. Patients received a routine bowel preparation in the morning followed by a helical abdominal computed tomography (CT) scan with air insufflation of the colon. The CT images were then processed by using surface-rendered software and interpreted by a single radiologist who was blinded to the clinical information. Colonoscopy was performed in the same afternoon without knowledge of the radiology results. All polyps and cancers were proven histologically. RESULTS: Five colorectal cancers were diagnosed and all were detected by virtual colonoscopy. The sensitivity and specificity of virtual colonoscopy for the detection of patients with polyps of all sizes, and patients with polyps >/=10 mm were 59, 92, 88 and 100%, respectively. The procedure was well tolerated by all patients. CONCLUSIONS: This study was carried out in a real clinical setting without a preselection of cases. Virtual colonoscopy was satisfactory for the detection of polyps greater than 10 mm, and for the diagnosis of cancer, and it is also a promising imaging modality for colorectal neoplasm detection in a Chinese population.

Colonic Polyps↗

Small invasive colonic cancer occurring in a hyperplastic polyp.

We report a case of advanced colon cancer which was supposed to have arisen from a hyperplastic polyp in a 68-year-old man. Colonoscopy revealed a depressed reddish area with a surrounding elevated lesion that was of a faded color compared with the normal mucosa. After the mucosal surface had been sprayed with crystal violet dye, magnifying colonoscopy showed an amorphous area in the central depression and the surrounding, slightly elevated lesion had an asteroid pattern. The depressed area was therefore considered to be a colonic cancer surrounded by a hyperplastic polyp. Endoscopic ultrasonography showed that the lesion was infiltrating further than the deep submucosal layer and it was therefore decided to treat the patient by laparoscopically assisted right hemicolectomy. The depressed lesion was found to be a well-differentiated adenocarcinoma invading the muscularis propria (diagnosed as IIc + IIa-like advanced adenocarcinoma). The surrounding flat elevated lesion was found to be hyperplastic mucosa. No adenomatous lesions were found. There have been few reported cases in which a preoperative diagnosis of carcinoma in a hyperplastic polyp has been made, but the possibility of carcinogenesis from hyperplastic polyps has come under consideration recently. This case was considered to be important because it raises the possibility that nonpolypoid cancer can develop from a hyperplastic polyp.

Adenocarcinoma↗