Three randomized long-term surveillance trials in patients with sporadic colorectal adenomas

Objective. Guidelines for surveillance of patients with previous sporadic colorectal adenomas are based on retrospective long-term follow-up and prospective short-term studies. The aim of the present studies was to compare relative risk (RR) of new neoplasia as well as complications, using different intervals between examinations in long-term surveillance. Material and methods. Between l98l and l991, patients with pedunculated and small, flat and sessile adenomas were allocated at random to a 24 months (group A) or 48 months (group B) interval between surveillance colonoscopies (n=671). Patients with flat and sessile adenomas greater than 5 mm in diameter were randomized to intervals of 6 months (group C) or 12 months (group D) between l981 and 1987 (n=73). Finally, 200 patients with similar adenomas as in groups C and D were randomized to 12 months (group E) or 24 months (group F) from 1988 to 2000. The study ended in 2002. Results. Advanced adenomas were equally as frequent in group A and group B, but colorectal cancer (CRC) was found significantly more often in group B (RR?=?6.2 (1.0–117.4)). Severe complications occurred in 4 patients in group A and 2 patients in group B. Advanced new adenomas tended to be more frequent in group D than in C (p=0.08), but only one CRC was detected and this was in group C. There was no significant difference in the risk of CRC between the E and F groups, but the two cancers in group E were both early stage, in contrast to those in group F. Severe complications were seen in one patient in group E and also in group F. Conclusions. The results suggest that 2-year intervals should be used between colonoscopies in patients with previous pedunculated adenomas and small, flat and sessile adenomas, whereas larger, flat and sessile adenomas may need intervals of 1 year.     

Three randomized long-term surveillance trials in patients with sporadic colorectal adenomas

OBJECTIVE: Guidelines for surveillance of patients with previous sporadic colorectal adenomas are based on retrospective long-term follow-up and prospective short-term studies. The aim of the present studies was to compare relative risk (RR) of new neoplasia as well as complications, using different intervals between examinations in long-term surveillance. MATERIAL AND METHODS: Between l98l and l991, patients with pedunculated and small, flat and sessile adenomas were allocated at random to a 24 months (group A) or 48 months (group B) interval between surveillance colonoscopies (n=671). Patients with flat and sessile adenomas greater than 5 mm in diameter were randomized to intervals of 6 months (group C) or 12 months (group D) between l981 and 1987 (n=73). Finally, 200 patients with similar adenomas as in groups C and D were randomized to 12 months (group E) or 24 months (group F) from 1988 to 2000. The study ended in 2002. RESULTS: Advanced adenomas were equally as frequent in group A and group B, but colorectal cancer (CRC) was found significantly more often in group B (RR = 6.2 (1.0-117.4)). Severe complications occurred in 4 patients in group A and 2 patients in group B. Advanced new adenomas tended to be more frequent in group D than in C (p=0.08), but only one CRC was detected and this was in group C. There was no significant difference in the risk of CRC between the E and F groups, but the two cancers in group E were both early stage, in contrast to those in group F. Severe complications were seen in one patient in group E and also in group F. CONCLUSIONS: The results suggest that 2-year intervals should be used between colonoscopies in patients with previous pedunculated adenomas and small, flat and sessile adenomas, whereas larger, flat and sessile adenomas may need intervals of 1 year.     

舒林酸治疗散发性结直肠腺瘤的临床研究

目的观察舒林酸对散发性结直肠腺瘤的疗效.方法 36例经结肠镜和组织学诊断的散发性结直肠腺瘤病人,随机分为二组,治疗组口服舒林酸400 mg/d,对照组口服安慰剂2片/d,疗程均为4个月.观察治疗前和治疗4个月时腺瘤数目、最大直径、形态及腺瘤异型增生分级变化.结果治疗组和对照组各16例完成试验.治疗前、后比较,治疗组59个腺瘤直径分别为(3.6±2.2)和(2.4±1.5)mm,治疗后腺瘤直径较治疗前明显缩小,差异有非常显著性(P＜0.001);腺瘤形态较治疗前变化明显,出现扁平隆起和红斑.异型增生级别明显降低,差异有非常显著性(P＜0.001);对照组30个腺瘤直径分别为(4.6±2.5)和(3.     

Clinical study of sulindac in the treatment of sporadic colorectal adenomas

OBJECTIVE: To investigate the efficacy of sulindac in the treatment of sporadic colorectal adenomas. METHODS: Thirty‐six patients who were diagnosed colonoscopically and pathologically with sporadic colorectal adenomas were randomly divided into two groups. The sulindac group took 400 mg sulindac daily for 4 months and the patients in the control group were given a placebo treatment for the same period of time. All patients underwent pancolono­scopy at the end of the study. The number, size, morphology, and degree of atypia of the adenomas were compared before and after treatment. RESULTS: Four patients were dropped from the study (three in the sulindac group, one in the control group). Sixteen patients in each group completed the trial. In the sulindac group, the average diameter of 59 adenomas before treatment was 3.6 ± 2.2 mm, which was significantly larger than that after treatment (2.4 ± 1.5 mm; P < 0.001). The morphology of adenomas also changed significantly. The degree of atypia of adenomas also decreased after treatment (P < 0.001). No severe side‐effects of sulindac were found during the study. In the control group, the average diameters of adenomas before and after treatment were 4.6 ± 2.5 mm and 3.7 ± 2.2 mm, respectively. There was no significant difference between the average diameters of the adenomas before or after treatment (P > 0.05), nor was there any change in the morphology or the degree of atypia of the adenomas. CONCLUSIONS: Sulindac is effective in reducing the size and degree of atypia of adenomas. This trial demonstrated that sulindac has a regressive effect on sporadic colorectal adenomas. However, its long‐term effect remains to be tested.     

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.     

Increased prevalence of colorectal neoplasia in korean patients with sporadic duodenal adenomas: a case-control study

Background/Aims

Recent data from Western populations have suggested that patients with sporadic duodenal adenomas are at a higher risk for the development of colorectal neoplasia. In this study, we compared the frequency of colorectal neoplasia in patients with sporadic duodenal adenomas to healthy control subjects.

Methods

This retrospective case-control study used the databases of 3 teaching hospitals in Gyeonggi-do Province, South Korea. The colonoscopy findings of patients with sporadic duodenal adenomas were compared with those of age- and gender-matched healthy individuals who had undergone gastroduodenoscopies and colonoscopies during general screening examinations.

Results

Between 2001 and 2008, 45 patients were diagnosed endoscopically with sporadic duodenal adenomas; 26 (58%) of these patients received colonoscopies. Colorectal neoplasia (42% vs 21%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.1 to 7.4) and advanced colorectal adenoma (19% vs 3%; OR, 9.0; 95% CI, 1.6 to 50.0) were significantly more common in patients with sporadic duodenal adenomas than in healthy control subjects.

Conclusions

Compared with healthy individuals, patients with sporadic duodenal adenomas were at a significantly higher risk for developing colorectal neoplasia. Such at-risk patients should undergo routine screening colonoscopies.     

Flat adenomas and flat adenocarcinomas of the colorectal mucosa in Japanese and Swedish patients

PURPOSE: In recent years, flat adenomas of the colorectal mucosa have been intensively investigated by Japanese pathologists. Results of that work indicate that flat adenomas may antedate the development of colorectal carcinomas. Because of differences in the Histologic definition of flat adenomas with severe dysplasia and with intramucosal carcinoma within the group, one single observer having both Western and Asian training in pathology reviewed the material. METHODS: A total of 287 flat colorectal lesions were reviewed: 109 from the Karolinska Hospital, Stockholm, 137 from the Tokyo Medical and Dental University (TMDU) (which included 50 cases from the Nagoya City University), and 41 from the Cancer Institute (CI), Tokyo. Lesions were histologically classified following strict Histologic criteria. Thus, flat adenomas were divided into those having lowgrade dysplasia (LGD; having dysplastic cells in the deeper half of the epithelium), high-grade dysplasia (HGD; dysplastic cells were found even in the superficial half of the epithelium), intramucosal carcinoma (dysplastic glands displayed molding with buddings and often a cribriform pattern), and adenocarcinoma (breaking through the muscularis mucosa, with neoplastic cells in the submucosal layer or deeper). RESULTS: Whereas in Stockholm only 14.7 percent of lesions had HGD, as much as 56.9 percent and 56.1 percent, respectively, had HGD at the two Tokyo Hospitals. Intramucosal carcinomas were not found in the Stockholm material but occurred in 2.2 percent of lesions seen at TMDU and in 4.9 percent of those seen at the CI. Notably, only 2.7 percent of the specimens at Karolinska Hospital had invasive adenocarcinoma, but it was seen in as many as 4.4 percent at TMDU and 21.9 percent at the CI. CONCLUSIONS: This study indicates that there were Histologic differences between flat neoplasias of the colorectal mucosa harvested in Stockholm and Tokyo. In Japan, lesions were obviously more advanced (in terms of HGD) and more aggressive (in terms of intramucosal and submucosal invasion). The cause for the differences found in those two disparate geographic regions remains poorly understood. The results, however, may help us understand some of the unclear points and discussions appearing in the literature on this subject.     

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.     

Frequency of polyps in patients undergoing surgery for colorectal cancer

INTRODUCTION: Epidemiologic and molecular biologic studies have already demonstrated that adenomatous colonic polyps are precancerous diseases. The main indication of the colonoscopy in the surveillance of colorectal cancer treated patients is the diagnosis and resection of adenomatous polyps. AIM: To study the frequency of adenomatous polyps after surgically resection of colorectal cancer. MATERIAL AND METHODS: Sixty eight patients, mean age 59 years old, with total resection of colorectal cancer, submitted to various colonoscopies during the follow up were studied retrospectively. The histological type and the characteristics of the polyp were described. RESULTS: The frequency of polyps was 18%, being higher in the patients with more than 45 years (20%). The site of the polyps was in the left colon in 38% of the patients with cancer. The histological type of adenomas was tubular in 61%, villous in 22% and mixed in 17%. DISCUSSION: As described by other authors, the incidence of polyps were higher after 45 years old and more than a half of them were tubular. The frequency of polyps was higher in the first two years of follow up.     

AMACR is associated with advanced pathologic risk factors in sporadic colorectal adenomas

AIM: To analyze α-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-f ive cases of sporadic colorectal adenomas were categorized according to the Vienna classif ication for Gastrointestinal Neoplasia.These corresponded to a total of 98 different intra-lesion microscopic f ields that were further independently assigned a histological grade based on the old nomenclature (mild,moderate,severe ...     

High frequency of K-ras mutations in sporadic colorectal adenomas.

The frequency of activating mutations at codons 12 and 13 of the K-ras gene was investigated in 57 sporadic adenomas from 47 patients using the polymerase chain reaction and oligonucleotide hybridisation assay. Sixty eight per cent of the adenomas tested were positive for K-ras mutations. This high frequency, combined with the lack of a correlation between mutations and adenoma size, suggest that K-ras mutations occur earlier in the adenoma-carcinoma sequence than has previously been suggested. The high frequency observed in sporadic adenomas contrasts with the reported low frequency (18%) in adenomas from patients with familial adenomatous polyposis (FAP), suggesting a possible difference in the molecular genesis of FAP and non-FAP adenomas. Finally, it was found that adenomas from patients with a personal history of colorectal cancer were more likely to contain a K-ras mutation than those from patients with no such history. This is a new finding and worthy of further study.     

Faecal unconjugated bile acids in patients with colorectal cancer or polyps.

The unconjugated faecal bile acid profiles of 14 patients with colorectal cancer, nine patients with polyps and 10 controls were compared using gas liquid chromatography, controlling for such confounding variables as cholecystectomy, gall stones and hepatic function. Patients with adenomatous polyps had a higher concentration of faecal bile acids (5.23 mumol/g, 2.16-13.67 (median, range) v 1.96, 0.91-6.97; p = 0.016) lithocholic acid (2.41, 0.88-3.22 v 1.07, 0.38-2.03; p = 0.013) and total secondary bile acids (5.23, 2.16-13.4 v 1.96, 0.73-6.63; p = 0.02) compared with control subjects. Patients with colorectal cancer had an increased (p = 0.029) proportion of secondary faecal bile acids (mol%) compared with controls (100, 96.5-100 v 95.19, 81.73-100) and the ratios of the primary bile acids, cholic and chenodeoxycholic acid, to their respective derivatives (secondary bile acids) were significantly lower in cancer patients compared with control and patients with polyps (p = 0.034 to 0.004). This study lends further support to the theory that bile acids may play a role in the development of polyps and colorectal cancer.