M. Osnes

Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years.

BACKGROUND, AIMS, AND PATIENTS: In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis of redetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. RESULTS: Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net regression in size, both for adenomas and hyperplastic polyps. This pattern was verified by computerised image analysis. Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients, and the same was true for those with multiple adenomas (four to five) compared with those with a single adenoma. The new adenomas were significantly smaller and 71% were located in the right side of the colon. Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma. One patient developed an invasive colorectal carcinoma, which may be evolved from a previously overlooked polyp. Two polyps, showing intramucosal carcinoma after follow up for three years, were completely removed, as judged by endoscopy and histological examination. CONCLUSIONS: The results show that follow up of unresected colorectal polyps up to 9 mm is safe. The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice. The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer.

Endoscopic retrograde cholangiography and endoscopic papillotomy in patients with a previous Billroth-II resection.

Methods for endoscopic retrograde cholangiography (ERC) and endoscopic papillotomy (EPT) in patients with Billroth-II operations are described, and experience with their use during the last four years (since 1980) is presented. Endoscopic retrograde cholangiopancreatography was successful in 134 of 147 patients (92%) and endoscopic papillotomy was successful in 46 of 50 patients. The described methods were used in two different hospitals by two different endoscopists and there was no difference in the results. We conclude that patients with a Billroth-II operation may undergo endoscopic diagnostic as well as therapeutic procedures with a high rate of success, with similar results as in ordinary patients and with no greater risk of complications.

Growth of Colorectal Polyps: Recovery and Evaluation of Unresected Polyps of Less Than 10 mm, 1 Year after Detection

BACKGROUND AND METHODS Colonoscopic 1-year control of polyps of less than 10 mm left in situ was carried out in 103 (89%) of 116 originally examined patients. RESULTS Analysis showed an 85% recovery: 91% and 81% for polyps of 5-9 mm and < 5 mm, respectively. The recovery was significantly related to size and localization, whereas the growth rate was inversely correlated to the originally measured diameter. A linear relationship was demonstrated between anus-to-polyp distances 1 year apart, with a normalized agreement index of 0.70. In only 1 of 189 polyps, an increase of diameter to > 10 mm was demonstrated. The 79 new polyps in 52 (50%) of the patients were significantly smaller, more often right-sided, and related to multiplicity of polyps at the initial examination but not to growth of recovered polyps or cleansing status. CONCLUSION An acceptable recovery and growth rate of polyps < 10 mm seems to justify the continuation of the study for the remaining 2 years.

Symptoms in Patients with Peptic Ulcer and Hematemesis and/or Melena Related to the Use of Non-Steroid Anti-Inflammatory Drugs

One hundred and seven consecutive patients with hematemesis and/or melena and a diagnosis of duodenal, gastric, or esophageal ulcers were interviewed immediately before or after endoscopy about the use of non-steroid anti-inflammatory drugs (NSAIDs) and symptoms before the hemorrhage. If the patients admitted no symptoms of abdominal pain or discomfort, nausea, vomiting, or heartburn, they were classified as having no ulcer symptoms before the hemorrhage. Patients who had not taken NSAIDs during the last 48 h before the hemorrhage were classified as not having taken NSAIDs. Significantly fewer patients had ulcer symptoms in the group that had used NSAIDs than in the other group (p less than 0.01). This may be interpreted as a possible masking effect by NSAIDs on ulcer symptoms. Physicians and patients should be aware of this possible effect of NSAIDs.

Comparison of the gastrointestinal side effects of naproxen formulated as plain tablets, enteric-coated tablets, or enteric-coated granules in capsules.

We studied the gastrointestinal side effects of three formulations of naproxen in 18 healthy male volunteers. In a Latin-square design crossover study, the subjects received 500 mg naproxen twice daily for 7 days as plain tablets, enteric-coated tablets, or enteric-coated granules in capsules. The 51Cr-EDTA absorption test was performed before and at the end of each drug period, to evaluate changes in the distal gut. The test dose was instilled distally in the duodenum to prevent lesions in the stomach from interfering with the evaluation. Upper endoscopy was performed at the same intervals, scoring changes in the middle and distal duodenum separately from findings in the stomach and duodenal bulb. The nature and severity of adverse effects were recorded for each treatment period. Non-parametric methods were used for statistical evaluation. All drugs induced a significant increase in 51Cr-EDTA absorption, but we did not detect any difference between the three formulations. All formulations were associated with a significant increase in all the endoscopic findings monitored. Enteric-coated tablets induced significantly less lesions than enteric-coated granules in the stomach and duodenal bulb, and an advantage over plain tablets was indicated. No difference was seen in the middle and distal duodenum. The proximal endoscopic scores were not correlated to those found in the middle and distal duodenum. Evaluation of the small and large bowel should probably be included in clinical studies of NSAIDs, but our findings suggest that the importance of transfer of mucosal lesions to the distal gut by enteric coating may have been overemphasized.

Reliability of in situ Measurements of Colorectal Polyps

A reliable and sensitive in situ method for measuring polyp size is fundamental for growth studies of colonic polyps. A measuring probe inserted through a colonoscope can give a visual assessment of polyp diameter, and from a picture of the polyp the area of the polyp on the picture can be calculated by computerized analysis. To test the reliability and sensitivity of these two in situ measurements, 43 colonic polyps (mean diameter, 8.5 mm; range, 4-20 mm) removed by snare diathermy resection were examined. The maximal diameter was measured, and two Polaroid pictures taken of each polyp. After polypectomy each polyp was subjected to extracorporeal reassessment of diameter and measurement of weight and volume. By computerized analysis of the pictures the following variables were estimated: 1) area of the polyp on the picture; 2) largest diameter; 3) maximum width 90 degrees on the largest diameter; 4) maximum distance from centre of gravity; and 5) minimum distance from centre of gravity. Results showed good correlation between diameter measured in situ and after removal (r = 0.93), diameter raised to the 3rd power and weight (r = 0.93), and also to volume (r = 0.77). Area analysis compared with weight was less good (r = 0.72). A very high correlation was demonstrated between weight and volume (r = 0.99). We conclude that the measurement of diameter in situ with a measuring probe is sensitive and somewhat more reliable than computerized analysis of size. The present 3-year follow-up and intervention study will show which of the two methods is preferable for evaluation of polyp growth.

Visual Analogue Scales for Endoscopic Evaluation of Nonsteroidal Anti-Inflammatory Drug-Induced Mucosal Damage in the Stomach and Duodenum

The use of visual analogue scales in the evaluation of mucosal lesions may reduce sample size requirements in clinical trials, but they may be complex to use, and adding guide points may reduce their informative value. We found that two investigators with differing levels of endoscopic experience reached comparable conclusions in 4 clinical trials (738 scores), and their scores were highly correlated, with similar dispersion characteristics. With guide texts along the scales, thus avoiding points on the actual scales, no tendency towards accumulation was seen in 1449 scores. These results encourage the use of visual analogue scales in endoscopic studies.

Cimetidine Tablets or Suspension for the Prevention of Gastrointestinal Mucosal Lesions Caused by Non-steroidal, Anti-inflammatory Drugs

We compared the protection offered by cimetidine 400 mg b.i.d. as tablets or suspension vs. placebo, in Naproxen-induced gastrointestinal damage in 17 healthy males. Upper endoscopy was performed before and after each drug period, with separate evaluation of duodenal mucosa distal to the duodenal bulb. 51Cr-EDTA absorption tests were done to assess distal mucosal integrity, and symptoms were registered. All regimens caused a significant increase in mucosal damage (p less than 0.01). Cimetidine tablets gave a significantly lower damage score than placebo for gastritis/duodenitis and hemorrhagic lesions in the stomach/duodenal bulb, and for the sum of scores in both scoring regions (p = 0.02). Cimetidine suspension was not significantly different from placebo for any of the endoscopic parameters. The 51Cr-EDTA absorption was significantly increased after all drug periods. However, there was no difference between the three drug combinations. Symptoms reported were mild and equal in the three groups. Cimetidine tablets offered protection against Naproxen-induced mucosal damage, primarily in the stomach and duodenal bulb, but lacked any effect on permeability changes. Cimetidine suspension was not significantly different from placebo in any respect.

Sucralfate for Prevention of Naproxen-induced Mucosal Lesions in the Proximal and Distal Gastrointestinal Tract

To study the protective effect of Sucralfate on Naproxen-induced mucosal lesions, 16 healthy, male volunteers were given Naproxen 500 mg b.i.d. together with Sucralfate 2 g b.i.d. or placebo in a double-blind, crossover study. Drug periods were 1 week, with a 3-week wash out in between. Mucosal lesions in stomach and duodenum were assessed by upper endoscopy before and after each drug period, using a visual analogue with separate scoring of mid- and distal duodenal lesions. 51Cr-EDTA absorption tests were performed to demonstrate possible changes in distal gut permeability. In addition, subjective symptoms were registered. Both drug periods induced significant lesions in the stomach and duodenum. Statistically speaking, fewer changes were found in the stomach and duodenal bulb after Sucralfate co-administration, whereas no significant reduction of lesions was seen in the distal duodenum. The 51Cr-EDTA absorption was increased in both periods, indicating deleterious effects to distal parts of the gut, but our results did not demonstrate Sucralfate-mediated protection from these changes. Symptoms were modest, and equal in the two periods. We conclude that Sucralfate may offer protection in the gastric and proximal duodenal mucosa, but no such protective effect was seen distally to the duodenal bulb.

Optimal Assessment of Gastrointestinal Side Effects Induced by Non-Steroidal Anti-Inflammatory Drugs: Endoscopic Lesions, Faecal Blood Loss, and Symptoms Not Necessarily Correlated, As Observed after Naproxen and Oxindanac in Healthy Volunteers

Gastrointestinal side effects caused by naproxen and oxindanac (a developmental non-steroidal anti-inflammatory drug) were compared by combined endoscopy and determination of faecal blood loss in 16 healthy male volunteers in a randomized, double-blind, crossover study. Individual daily faecal blood loss was determined by means of 51Cr-labelled erythrocytes. Gastroduodenoscopy was performed before and after administration of naproxen, 750 mg/day, and oxindanac, 600 mg/day, for 1 week each. A washout period of at least 3 weeks was inserted between drug periods. Visual analogue scales (VAS) were used for endoscopic assessment of lesions and subjective complaints. Mean faecal blood loss increased from a base line 0.48 ml/24 h to 1.59 ml/24 h with naproxen (p less than 0.01) and from 0.56 ml/24 h to 1.31 ml/24 h with oxindanac (p less than 0.01). VAS scores for gastroduodenal lesions increased significantly with both drugs. Naproxen caused a significantly greater increase than oxindanac (p less than 0.05). There was no correlation between gastrointestinal blood loss and endoscopic findings. Subjective symptoms were correlated to faecal blood loss with naproxen, but not to endoscopic findings. No such correlations were observed for oxindanac. Naproxen caused a significant prolongation of bleeding time (p less than 0.01), whereas the increase caused by oxindanac was not significant (p = 0.09).