Ileostomy polyps, adenomas, and adenocarcinomas.

Ileostomy polyps are uncommon and poorly described. The aim of this study was to undertake a retrospective clinicopathological review of ileostomy polyps. Seven patients with 60 polyps arising on ileostomies performed for ulcerative colitis were studied. The histopathological evaluation of archival ileostomy biopsy specimens, polypectomy or excision specimens, and clinical review of patient records was undertaken. Fifty of 60 polyps were inflammatory cap polyps and six further polyps were composed of granulation tissue only. They occurred anywhere on the stoma at any time after ileostomy construction and were strongly associated with overt stomal prolapse. Four neoplastic polyps were identified in two patients 27-36 years after ileostomy construction; all occurred at the mucocutaneous junction. One patient presented with a 2 cm polypoid invasive adenocarcinoma while in the second a 1.7 cm polypoid mucinous adenocarcinoma and a 0.7 cm ileal tubular adenoma with high grade dysplasia occurred at the site of excision of a cap polyp showing focal low grade adenomatous dysplasia six years previously. Neoplastic and non-neoplastic polyps could not be differentiated clinically. It was found that most ileostomy polyps are inflammatory cap polyps associated with stomal prolapse. Less common are polypoid adenomas or adenocarcinomas arising at the mucocutaneous anastomosis > 20 years after ileostomy construction. To prevent ileostomy carcinoma it is recommended that a biopsy of all polyps at the mucocutaneous anastomosis and of any non-prolapse associated polyps elsewhere on the stoma occurring > 15 years after ileostomy construction is done.     

Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission.

BACKGROUND: The histogenesis of human colorectal hyperplastic polyps and colorectal adenomas is poorly understood even now. METHOD: Human colorectal adenomas, hyperplastic polyps, and normal colorectal mucosae (patients with familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma were excluded) were obtained during colonoscopy and microdissected into individual crypts. Morphology, cell proliferation characteristics, and fission indices of crypts isolated from these lesions were then studied. RESULTS: Crypts isolated from colorectal adenomas and colorectal hyperplastic polyps were significantly larger (p<0.001) than crypts from normal colorectal mucosae. Crypt fission was an uncommon event in normal colonic mucosae but common in crypts isolated from adenomas and hyperplastic polyps (p<0.001). Analysis of the distribution of mitoses suggested an upward expansion of the proliferation compartment in adenomas to the surface of the crypt with no reversal of proliferating cell distribution, as has previously been described. CONCLUSIONS: Sporadic human colorectal adenomas and hyperplastic polyps grow by the process of crypt fission. Expansion of the proliferative compartment was demonstrated in crypts from adenomas, consistent with deregulation of cell cycle control.     

Colon adenomas in patients with hyperplastic polyps

Although hyperplastic polyps are generally believed to have no malignant potential, recent work has suggested that they might be more common in patients with adenomas. We evaluated whether hyperplastic polyps could serve as a marker for patients who might benefit from colonoscopy. We retrospectively reviewed 1,588 consecutive colonoscopy reports and hospital charts on 1,407 different patients examined between May 1983 and August 1985: 242 patients had adenomas, and 94 had hyperplastic polyps. Of patients with hyperplastic polyps 93.6% had concomitant adenomas, as compared with 35.7% of those without, p less than 0.001. Adenomas proximal to the rectosigmoid were found in 61.7% of patients with hyperplastic polyps and in 25.3% of those without, p less than 0.001. Patients with hyperplastic polyps in the rectosigmoid had proximal adenomas more frequently (64.7%) than did those without rectosigmoid hyperplastic polyps (29.4%), p less than 0.001. We conclude that patients with hyperplastic polyps are more likely to have adenomas, and patients with rectosigmoid hyperplastic polyps are more likely to have proximal adenomas. Based on these preliminary data, we believe that the finding of hyperplastic polyps in the rectosigmoid might justify full colonoscopy and that this should be studied further.     

Colorectal hyperplastic polyps and risk of recurrence of adenomas and hyperplastic polyps. Polyps Prevention Study

We examined data from two large colorectal chemoprevention trials for possible associations of hyperplastic polyps and adenomas with subsequent development of these lesions. Hyperplastic polyps do not predict metachronous adenomas.     

Risk for colon adenomas in patients with rectosigmoid hyperplastic polyps

OBJECTIVE: To determine whether hyperplastic polyps found in the rectosigmoid area of the colon are associated with proximal adenomas, and to judge whether patients with distal hyperplastic polyps found during sigmoidoscopy might benefit from full colonoscopy. DESIGN: Data on patients having colonoscopy collected prospectively according to a set protocol. The size and location of all polyps were noted, and all polyps were biopsied. SETTING: Two university hospitals. PATIENTS: One thousand eight hundred and thirty-six consecutive patients referred for colonoscopy between 31 December 1987 and 31 August 1989. RESULTS: Of the 970 patients who met eligibility requirements, 274 (28.3%) had adenomas and 108 (11.1%) had hyperplastic polyps. The proportion of patients with distal hyperplastic polyps and proximal adenomas (31.9%) was similar to the proportion of those without distal hyperplastic polyps (23.0%) (crude odds ratio, 1.57; 95% CI, 0.77 to 3.06). After adjusting for age and sex, the results were unchanged (adjusted odds ratio, 1.53; CI, 0.82 to 2.88). Patients with distal adenomas, on the other hand, were three times more likely to have proximal adenomas than those without distal adenomas (adjusted odds ratio, 3.42; CI, 1.99 to 5.88). CONCLUSIONS: Distal hyperplastic polyps are not strong predictors of risk for proximal adenomas. Based on the magnitude of the risk difference, we do not believe that finding a hyperplastic polyp during sigmoidoscopy justifies doing a full colonoscopy to search for proximal adenomas. Because rectosigmoid adenomas are associated with proximal adenomas, however, small polyps seen during sigmoidoscopy should be biopsied to determine their type. Colonoscopy should be reserved for patients who are proved to have adenomas.     

Comparison of cyclo-oxygenase 2 expression in colorectal serrated adenomas to expression in tubular adenomas and hyperplastic polyps

BACKGROUND AND AIMS: Serrated adenoma (SA) is a newly defined category of colorectal neoplasia that contains features of both adenoma and hyperplastic polyp, and has two patterns, hyperplastic and cerebriform patterns. Since cyclooxygenase 2 (COX-2) has been found upregulated in colorectal cancers and adenomas, we examined whether either the hyperplastic or cerebriform pattern of SA has the potential for tumor progression and should be a target for clinical treatment. PATIENTS AND METHODS: An immunohistochemical scoring system was used to compare COX-2 expression in colorectal SAs (n=79), tubular adenomas (n=66), and hyperplastic polyps (n=21). RESULTS: COX-2 scores were significantly higher in SA of the cerebriform pattern (n=44) than in SA of the hyperplastic pattern (n=35). There was no difference in COX-2 scores between SA of the cerebriform pattern and tubular adenoma. In SA accompanied by hyperplastic polyp (n=26) the hyperplastic components expressed little COX-2, the same as traditional hyperplastic polyps. COX-2 expression in the SA component was similar to that in pure SA. CONCLUSION: SA of the cerebriform pattern should be treated similarly as traditional tubular adenomas. COX-2 induction may additionally be involved in progression from hyperplastic polyp to SA.     

Frequency of colorectal polyps in patients with sporadic adenomas or adenocarcinomas of the papilla of vater--an age-matched, controlled study

BACKGROUND: Epithelial tumors of the papilla of Vater are rare neoplasms of the gastrointestinal tract. The carcinogenesis of these tumors seems to be fairly analogous to the genetic mechanisms which have been described for colorectal carcinoma. Patients with familial adenomatous polyposis bear a particularly increased risk for periampullary tumors. Data on whether the prevalence of colorectal tumors is increased in patients with sporadic ampullary neoplasms are scarce. METHODS: 26 consecutive patients (16 women, 10 men; median age 59 years) with sporadic adenomas (n = 19) or adenocarcinomas (n = 7) of the ampulla of Vater were retrospectively evaluated. The study patients were compared with 104 age-matched asymptomatic controls. All patients had undergone total colonoscopy. RESULTS: Neoplastic colorectal polyps were present in a similar proportion (23%) of patients of the study group compared with 26% in the control group (p > 0.05). Overall, 16 polyps were found among patients with ampullary tumors and 40 in asymptomatic controls (p > 0.05). Colonoscopy detected rectal carcinoma in 2 patients (8%) of the study group. Patients with and without colorectal polyps differed neither significantly by age nor by ampullary histological findings. 50% of the colonic polyps in patients with ampullary neoplasms were located in the ascending colon. CONCLUSIONS: The frequency of colorectal polyps in patients with ampullary tumors did not exceed the risk in the control group. However, the finding of 2 rectal carcinomas among patients with ampullary neoplasms supports the place of screening colonoscopy for the diagnostic work-up of ampullary tumors. Prospective multicenter studies should address this issue to provide a broad basis for future recommendations.     

Histogenesis of hyperplastic polyps of the stomach in terms of cellular proliferation

We investigated the histogenesis of hyperplastic polyps of the stomach, in terms of cellular proliferation, by studying endoscopically removed and gastrectomized human gastric polyps either labeled with bromodeoxyuridine (BrdU) by in vitro flash labeling techniques or labeled in an isolated organ circulation system, in both of which, perfluorochemical artificial blood was employed. Immunohistochemistry with antibodies against BrdU and proliferating cell nuclear antigen (PCNA) was simultaneously employed. The generative cell zone of pedunculated and semipedunculated polyps was markedly expanded compared with that of the background mucosa, and this change also appeared in sessile polyps, although to a lesser degree. Enhanced proliferative activity was observed in both epithelial and stromal cells in areas of erosion. Our results demonstrate that the initial change in the histogenesis of hyperplastic polyps is an expansion of the generative cell zone, followed by interstitial edema and stromal cell proliferation, and that erosion can facilitate these changes. No correlation was found between the size of the polyps and the labeling indices. This finding explains, in part, the diversity of chronological changes in the size and shape of hyperplastic polyps.     

Prevalence and incidence of hyperplastic polyps and adenomas in familial colorectal cancer: correlation between the two types of colon polyps

BACKGROUND AND AIMS: Colorectal adenomas are recognised as precursors of colorectal carcinomas. The significance of hyperplastic (metaplastic) colorectal polyps is unknown. The relationship between hyperplastic polyps and adenomas, and the prevalence and incidence of these lesions were evaluated in individuals predisposed to familial colorectal cancer. METHODS: A total of 299 individuals participating in our surveillance programme during 1990-2000 were retrospectively evaluated. Subjects were classified into three groups: hereditary non-polyposis syndrome (HNPCC) (n=108), hereditary colorectal cancer (HCRC) (n=127), and individuals with empirical risk estimates-two close relatives (TCR) (n=64). Findings from 780 colonoscopies were evaluated regarding prevalence and incidence of hyperplastic polyps and adenomas. Correlations between hyperplastic polyps and adenomas were calculated by Pearson correlation. RESULTS: In total, 292 hyperplastic polyps and 186 adenomas were observed in 98 and 90 individuals, respectively. A positive correlation was found between the numbers of hyperplastic polyps and adenomas (r=0.40; p<0.001). Correlations between adenomas and hyperplastic polyps were similar in the three groups. The risk of detecting new hyperplastic polyps (odds ratio 5.41) or adenomas (OR 2.56) increased significantly when there was a positive finding at first colonoscopy. CONCLUSION: Hyperplastic polyps as well as adenomas may identify individuals with a high risk of colorectal cancer. This information is important when these individuals are selected and included in tailored surveillance programmes.     

Estrogen receptor protein in adenomas of the large bowel

Thirty adenomas of the large bowel, removed from 15 females and 15 males, were examined for the presence of estrogen receptor protein. The finding of positive binding capacity in two of the 30 adenomas supports the hypothesis that hormonal dependency does not play a major role in the development and growth of colorectal adenomas.     

Cholecystectomy and adenomatous polyps of the large bowel.

Seventy two patients (39 women) with colonic adenomas were compared with 72 adenoma free controls (39 women) to investigate the possible association between previous cholecystectomy and the subsequent development of adenomas. Data were gathered retrospectively from medical records. Overall there was no significant association between colonic adenomas and previous cholecystectomy. When women are considered separately, however, eight cases and no controls had undergone cholecystectomy (odds ratio infinity lower 95% confidence limits 1.7, p greater than 0.01). No association between previous cholecystectomy and large bowel adenomas was found in men. Four of nine (44.4%) women with right sided colonic adenomas had undergone previous cholecystectomy compared with only three of 23 (13%) women with left sided adenomas.     

Distal colonic hyperplastic polyps do not predict proximal adenomas in asymptomatic average-risk subjects.

The significance of distal colonic hyperplastic polyps was investigated in 482 asymptomatic average-risk subjects, aged 50-75 years, in whom fecal occult blood test results were negative and who underwent screening colonoscopy. The incidence of adenomas in the colon proximal to the sigmoid-descending colon junction in subjects with hyperplastic polyps distal to that point was 18% and was similar to the incidence of proximal colonic adenomas in subjects with no distal colonic polyps (15%). The incidence of proximal colonic adenomas in subjects with no distal colonic adenomas was 38% and was significantly greater than the incidence found in individuals with no distal colonic polyps or only hyperplastic polyps. Our data do not support distal colonic hyperplastic polyps as markers for proximal colonic adenomas in asymptomatic average-risk subjects.     

Pressure dye-spray: a simple and reliable method for differentiating adenomas from hyperplastic polyps in the colon

BACKGROUND: Based on 10 years of experience with chromoendoscopy, our hypothesis was that colonic adenomas can be differentiated from hyperplastic polyps by use of a high-pressure spray-jet of dye (pressure dye-spray). To test the accuracy of pressure dye-spray, classification of colonic polyps as adenomas and hyperplastic polyps by pressure dye-spray and ordinary colonoscopic findings (shape, size, and color surface appearance) were compared. METHODS: Pressure dye-spray chromoendoscopy was performed by using 0.035% indigo carmine, a spray-type cannula, and a water pump. Polyps were first classified as adenomas or hyperplastic polyps by ordinary colonoscopic findings. One or more pressure dye-spray bursts were then focused on the polyp from a distance of 1 to 2 cm. Polyps were classified as adenomas only if oozing of blood was evident; otherwise, they were classified as hyperplastic polyps. A histologic diagnosis was obtained for all polyps, and the results of ordinary colonoscopic findings and pressure dye-spray were compared. RESULTS: This study examined 1468 polyps (1201 adenomas, 267 hyperplastic polyps; mean diameter 4 mm). The sensitivities for polyp differentiation with pressure dye-spray and ordinary colonoscopic findings were, respectively, 97.9% and 73.4% (p < 0.0001); specificities were, respectively, 96.6% and 92.1% (p = 0.077). CONCLUSIONS: Pressure dye-spray was found to be a reliable technique for differentiation between adenomas and hyperplastic polyps.     

Comparative study of carcinoembryonic antigen and epithelial membrane antigen expression in normal colon, adenomas and adenocarcinomas of the colon and rectum.

The heterogeneous nature of tumour antigen expression may require selection of monoclonal antibodies on an individual patient or tumour basis to allow adequate tumour localisation. Carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression has not previously been compared in colorectal cancer patients. Sections of cancer (n = 52), adjacent normal colon (n = 45), synchronous adenomas (n = 11) and nodal metastases (n = 49) were examined by indirect immunoperoxidase staining in 51 consecutive patients with colorectal cancer using monoclonal antibodies to CEA and EMA. The percentage of cells with positive staining in the primary tumours was graded 1: less than 25%, 2: 25-49%, 3: 50-75%, 4 greater than 75%. All primary colorectal cancers expressed CEA and 43 of 52 expressed EMA (83%). Grading showed CEA greater than EMA in 39, equal in 11 and less in two. Well differentiated cancers were more frequently graded three or four for CEA staining (23 of 27) than moderately differentiated cancers (11 of 22) (p less than 0.01). Equivalent figures for EMA were four of 27 and three of 22 (not significant) (NS) although the majority (86%) were graded 1 and 2. Grade 1 CEA expression was found in six of 15 proximal and only two of 37 distal lesions (p less than 0.01, chi 2 test) while for EMA equivalent figures were three of 15 and six of 37 (NS). Nodal deposits all expressed CEA and 45 of 49 expressed EMA (92%); 29 of 45 normal colon sections showed CEA expression (64%) as did all adenomas. EMA was not expressed by normal colon or adenomas. These results suggest that EMA expression is more specific but less sensitive than CEA for colonic cancer and is independent of tumour differentiation and site. Thus selecting monoclonal antibodies to CEA or EMA based on tumour biopsies may allow improved tumour localisation for imaging or therapy in patents with colorectal cancer.     

Flat,hyperplastic, and sessile serrated polyps

Increasing evidence indicates that colonoscopy offers less reliable protection against proximal versus distal colorectal cancer. Two key factors may explain the occurrence of postcolonoscopy (ie, interval) cancers in the proximal colon, namely endoscopist-dependent factors and biological characteristics of precursor lesions resulting in a more rapid progression. There is increasing evidence that nonpolypoid lesions, of adenomatous or serrated type, are major contributors to interval cancers through endoscopist-dependent factors, as these lesions are preferentially located in the proximal colon and more likely to be overlooked and/or incompletely resected, in particular when predisposing factors (ie, suboptimal bowel preparation or insufficient training) are involved. However, emerging data now indicate that a subset of nonpolypoid adenomas might also display distinct molecular features that may impact on growth as compared with their polypoid counterparts. In this review, we summarize the current literature on classification and biological significance of nonpolypoid colorectal lesions, with special attention to their endoscopic appearance and potential implications for training.     

Quantitative electron microscopic study on grades of atypia in adenomas of the human large bowel

Clarification of the ultrastructural features of the three different grades of histologic atypia of adenomas (i.e., mild, moderate, and severe atypia) with reference to carcinoma of the human colon and rectum was undertaken using electron microscopic quantitative analysis. Ten normal epithelia, 36 adenomas (14 with mild atypia, 13 with moderate atypia, and 9 with severe atypia) and 14 carcinomas (well-differentiated adenocarcinoma) were examined with light and electron microscopes. Although it has been generally accepted that malignant transformation of an adenoma gradually proceeds with increasing atypia, using light microscopy, ultrastructural quantitative analysis clearly revealed that fine features of individual atypia did not correspond with histologic grades of atypia. Ultrastructural changes occurred abruptly in moderate atypia and showed similar cellular characteristics to carcinoma cells. Mild atypia was almost similar in appearance to normal epithelial cells. Striking changes in the moderate atypic cells were plane apposition of the cell membrane, decrease of the desmosomes, and increase of the lysosomes. These atypical cells were assumed to play a significant role in the adenoma-carcinoma sequence. Therefore, radical surgical therapy would be required for moderate atypic adenoma of the large bowel that is difficult to remove endoscopically