Barium enema and endoscopy for the detection of colorectal neoplasia: sensitivity, specificity, complications and its determinants.

AIM: To analyse sensitivity, specificity and complication rate of endoscopy, and barium enema for the detection of colorectal neoplasia. MATERIALS AND METHODS: A MEDLINE search was performed (1980-2000) directed at the endoscopic and radiologic literature on barium enema. Articles were selected based on the type of study, availability of sensitivity and specificity values in sizeable patient groups, and reports on complications. Sixty articles were included in the analysis. RESULTS: Endoscopy proved to have superior sensitivity for polyps in patients at high-risk for colorectal neoplasia. The role of endoscopy and radiology in average-risk screening populations is not known. Sensitivity and specificity rates ranged widely, probably due to bias. For the detection of small polyps endoscopy has superior performance, whereas sensitivity is similar for endoscopy and barium enema for the detection of larger (>1 cm) polyps and tumours. Overall, endoscopy is associated with a higher complication rate. CONCLUSION: Endoscopy is the preferred detection method in high-risk patients. The role of endoscopy and radiology in a screening setting requires evaluation. This review provides the test characteristics of endoscopy and radiology which are relevant for a cost-effectiveness analysis. Double-contrast barium enema may play an important role for screening purposes, owing to its good sensitivity for detecting larger (>1 cm) polyps and its lack of major complications. de Zwart, I. M.et al. (2001). Clinical Radiology56, 401-409.

Mesalazine-induced apoptosis of colorectal cancer: on the verge of a new chemopreventive era?

BACKGROUND: It is an accepted fact that non-steroidal anti-inflammatory drugs (NSAIDs) are potent inhibitors of colorectal carcinogenesis. However, the major disadvantages of NSAIDs are gastrointestinal and renal toxicity. We conducted a prospective pilot study on the effects of the safe salicylic acid derivative, mesalazine, on apoptosis and proliferation of tumour cells and on normal tissue in colorectal cancer patients. METHODS: Patients with colorectal cancer were asked to take mesalazine enemas for 14 days. Biopsies from malignant and normal tissue were taken prior to and after this treatment. Apoptosis was scored on haematoxylin/eosin-stained tissue sections, and cell proliferation was assessed by the proliferation marker Ki-67. RESULTS: Ten out of 14 patients completed the study. The apoptotic score increased significantly in the tumour samples (pre-treatment 14.6 +/- 1.3 vs. post-treatment 19.4 +/- 0.8; P < 0.03). The apoptotic index in the normal mucosa was unchanged (pre-treatment 3.1 +/- 0.4 vs. post-treatment 2.9 +/- 0.3; N.S.). The cell proliferation in malignant tissue, according to the Ki-67 score, was hardly affected by mesalazine (pre-treatment 522 +/- 38 vs. post-treatment 493 +/- 39; N.S.). There was no effect on the Ki-67 index of normal mucosa (pre-treatment 24.2 +/- 2.0 vs. post-treatment 28.3 +/- 2.0; N.S.). CONCLUSIONS: This pilot study conducted in patients with colorectal cancer clearly shows that mesalazine selectively induces apoptosis of tumour cells. On the basis of these findings, which need to be confirmed in larger studies, it may be speculated that 5-ASA could be useful in the chemoprevention of colorectal cancer.

Budesonide in inflammatory bowel disease.

Due to its immunomodulatory and anti-inflammatory properties glucocorticosteroids have proved to be highly efficacious in patients with inflammatory bowel disease. However, because of the risk of side-effects, the dose and duration of therapy with systemically acting glucocorticosteroids have to be restricted. Recently the use of topically acting glucocorticosteroids has attracted great interest. Among the various topically acting glucocorticosteroids budesonide has emerged as the most promising. Budesonide is highly potent, is readily water-soluble and has low systemic bioavailability, thus reducing the risk of corticosteroid-related side-effects. When given as enema to patients with proctitis or proctosigmoiditis, the efficacy of budesonide is greater than that of placebo and equal to that of prednisolone or 5-aminosalicylic acid enemas. In an enteric-coated formulation budesonide is more effective than placebo in achieving and maintaining remission in patients with ileocecal Crohn's disease. Although corticosteroid-related side-effects are rare, some suppression of the hypothalamic-pituitary-adrenal axis may occur.

Hereditary nonpolyposis colorectal cancer: results of long-term surveillance in 50 families.

A surveillance programme comprising either colonoscopy of sigmoidoscopy plus barium enema every 2-3 years was instituted in 50 hereditary nonpolyposis colorectal cancer (HNPCC) families. The families included 238 patients with colorectal cancer (CRC) (mean age at diagnosis: 43.7 years; range: 16-86 years). These patients had 597 first-degree relatives of whom 493 could be traced and 388 (79%) accepted the invitation for screening. The control group were relatives (index patients) with symptomatic CRC. The average follow-up duration was 5 years (1-20 years). Screening led to the detection of adenomas in 33 patients and CRC in 11 patients. Pathological examination revealed 1 Dukes' A, 7 Dukes' B and 3 Dukes' C cancers. In contrast, among the control group 47% had advanced CRC (Dukes' C or distant metastases). The 5-year survival of the screen-detected cases was 87% versus 63% in the control group. Of the 11 CRC cases in the screening group, 4 were detected within 1-4 years after a negative colonic examination. A large proportion of the polyps found in the screening and control groups showed a villous growth pattern and/or a high degree of dysplasia. We conclude that periodic examination of HNPCC families allows the detection of cancer at an earlier stage than in patients not under surveillance. Because of the possibly more aggressive nature of polyps associated with HNPCC, we recommend a screening interval of 1-2 years.

Effect of oral zinc supplementation on metallothionein and superoxide dismutase concentrations in patients with inflammatory bowel disease.

Oxygen-derived free radicals may contribute to intestinal tissue damage in inflammatory bowel disease. The concentrations of metallothionein and superoxide dismutase, two copper and zinc containing proteins involved in the scavenging of free radicals; were previously found to be decreased in the intestinal mucosa of patients with this disorder. The plasma zinc concentration is often decreased also in these patients. Since zinc is reported to be an efficient inducer of metallothionein synthesis, and probably of superoxide dismutase, we evaluated the effect of oral zinc supplementation on metallothionein and superoxide dismutase levels in patients with inflammatory bowel disease. Fourteen patients with inactive to moderately active inflammatory bowel disease received oral zinc supplementation (300 mg zinc aspartate, equal to 60 mg elemental zinc per day) for 4 weeks in a placebo-controlled double-blind cross-over trial. The plasma zinc concentration of these patients was low at the start of the study (12.2 +/- 1.7 mumol/L, P < 0.05), when compared to that of 22 healthy controls (13.6 +/- 2.3 mumol/L), but increased (P < 0.05) towards the levels of controls during the supplementation period (13.3 +/- 2.5 mumol/L). The concentrations of metallothionein and superoxide dismutase in plasma and in erythrocytes did not change in relation to the supplementation. The metallothionein concentration in both inflamed and non-inflamed intestinal mucosa was slightly higher after zinc supplementation but the superoxide dismutase concentration in the tissue was not altered. The histological inflammation score of intestinal biopsies, plasma albumin levels, and the disease activity index of the patients did not change during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased prevalence of colonic adenomas in patients with acromegaly.

Forty-nine acromegalics and 57 controls matched for age and sex underwent colonoscopy. The control group consisted of patients investigated because of atypical abdominal complaints compatible with irritable bowel syndrome or constipation. The exclusion criteria for both groups included: age over 75 years, previous colonic polyps or cancer, previous colonic surgery, rectal blood loss, anemia, previous abdominal radiation, sigmoidoscopy, colonoscopy or barium enema performed for any indication within 3 years prior to the present study. Colonoscopy was successful in reaching the cecum in 72 and 77% of the controls and acromegalics, respectively (p = NS). Eleven (22%) of 49 acromegalics had biopsy-proven colonic adenomas versus only five (9%) of the control group (p < or = 0.05). Multiple adenomas were found in three of the 11 acromegalics and in none of the controls. In five of these 11 patients and in only one of the controls, at least one adenoma was located in the right colon. In addition, acromegalics tended to have larger adenomas. The group of acromegalics with and without adenomas did not differ significantly in age or duration of active disease. In conclusion, the present study shows that acromegalic patients have an increased risk of developing colonic adenomas.

Colorectal adenomas: clinical and morphological aspects. A review of 166 polyps from 124 Dutch patients.

In a series of 124 consecutive Dutch patients the clinical and morphological features of 166 endoscopically removed colorectal adenomatous polyps were reviewed. The most frequent clinical symptom was manifest blood loss with the stools (51%), but no specific adenoma symptom seemed to exist. Barium enema X-ray examination was done in 108 patients, whereas all patients were colonoscoped. The routinely performed barium examinations detected 71% of the polyps that were found during endoscopy, but not all X-ray examinations were air contrast barium enemas. A good correlation between the localization of the adenomas after both diagnostic modalities was found, indicating that more than 80% were located in the left part of the colon. Nineteen percent of the patients had had a metachronous (pre)neoplastic lesion removed from their large bowel previously, while 40% of the patients had a synchronous polypoid lesion at the moment of polypectomy. Sixty-two percent of the adenomas were tubular, whereas 38% were villous adenomas. There was a strong correlation between size and villous architecture (r = 0.38; p less than 0.001). The epithelial dysplasia was mild in 21%, moderate in 70% and severe in 9% of the adenomas. The degree of dysplasia correlated well with the villous type of mucosal growth (r = 0.24; p less than 0.005). These findings indicate that, 1) there are no colorectal adenoma specific symptoms, 2) to detect colorectal adenomas colonoscopy is the investigation of choice, 3) after the detection of a colorectal adenoma the whole colon should be investigated, 4) colorectal adenoma patients should be kept under surveillance, and 5) determination of the diameter and of the degree of epithelial cell dysplasia may be helpful in assessing the biological behavior of an adenomatous polyp.