Biomedical subjects
B J Rembacken
Publications and source records attributed to B J Rembacken.
Endoscopic mucosal resection.
We are now finding more malignancies in their early stages than previously. Attempts to ablate these lesions are difficult and do not provide the histological information required to decide on further treatment. Surgery is difficult to justify, as only a minority of lesions are associated with lymph node metastases and lesions may not become clinically relevant within the lifetime of an elderly patient. Endoscopic mucosal resection allows cancers to be resected at minimal cost, morbidity and mortality. It is also the most reliable investigation when assessing lesions which are suspicious for containing early cancer. After endoscopic removal, histological assessment of depth of penetration and a search for invasion into lymphatics or venules allows the risk of microscopic lymph node metastases to be predicted. The risk of developing metastatic disease can then be balanced against the risks of surgery in view of the patient's age and health.
Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK.
BACKGROUND: Flat and depressed colorectal tumours were originally thought to be unique to the Japanese population. Recently there have been reports of flat and depressed lesions in western countries but they have been thought to be uncommon. METHODS: In this prospective study, 1000 consecutive patients attending for routine colonoscopy were examined for flat or depressed lesions. The examinations were done by one European colonoscopist using methods developed in Japan. FINDINGS: 321 adenomas were found: 202 (63%) were polypoid, 36% (117) were flat and 2 (0.6%) appeared depressed. Most adenomas contained areas of mild or moderate dysplasia but 10% (31) were severely dysplastic. Six Dukes' A adenocarcinomas were identified together with 25 more advanced adenocarcinomas. The likelihood of Dukes' A cancer or severe dysplasia increased from 4% (3/70) in small flat lesions, to 6% (9/154) in small polyps, 16% (8/50) in larger polyps, 29% (14/49) in large flat lesions, and 75% (3/4) in depressed lesions. 54% (20/37) lesions containing severe dysplasia or Dukes' A carcinoma were flat or depressed. INTERPRETATION: The polyp-carcinoma hypothesis prompts colonoscopists to search only for polypoid lesions when screening for cancer, and many early colorectal neoplasms may therefore be missed. Colonoscopists require training in the recognition of flat and depressed lesions to detect colorectal tumours in the early stages.
Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial.
BACKGROUND: Ulcerative colitis has been suggested to be caused by infection and there is circumstantial evidence linking Escherichia coli with the condition. Our aim was to find out whether the administration of a non-pathogenic strain of E. coli (Nissle 1917) was as effective as mesalazine in preventing relapse of ulcerative colitis. We also examined whether the addition of E. coli to standard medical therapy increased the chance of remission of active ulcerative colitis. METHODS: This was a single-centre, randomised, double-dummy study in which 120 patients with active ulcerative colitis were invited to take part. 116 patients accepted; 59 were randomised to mesalazine and 57 to E. coli. All patients also received standard medical therapy together with a 1-week course of oral gentamicin. After remission, patients were maintained on either mesalazine or E. coli and followed up for a maximum of 12 months. A two-stage, conditional, intention-to-treat analysis was done. FINDINGS: 44 (75%) patients in the mesalazine group attained remission compared with 39 (68%) in the E. coli group. Mean time to remission was 44 days (median 42) in the mesalazine group and 42 days (median 37) for those treated with E. coli. In the mesalazine group, 32 (73%) patients relapsed compared with 26 (67%) in the E. coli group. Mean duration of remission was 206 days in the mesalazine group (median 175) and 221 days (median 185) in the E. coli group. INTERPRETATION: Our results suggest that treatment with a non-pathogenic E. coli has an equivalent effect to mesalazine in maintaining remission of ulcerative colitis. The beneficial effect of live E. coli may provide clues to the cause of ulcerative colitis.
Flat adenomas in the United Kingdom: are treatable cancers being missed?
BACKGROUND AND STUDY AIMS: The recognized pathway for colorectal malignancies is the adenoma-carcinoma sequence. It is estimated that up to two-thirds of colorectal carcinomas arise from adenomatous polyps. In recent years, Japanese workers have suggested that early colorectal malignancies may arise as "flat" or "depressed" rather than as polypoid lesions. Such flat or depressed adenomas and adenocarcinomas have not been widely recognized in the West. A prospective study was carried out to search for flat and depressed adenomas in a British population, using Japanese colonoscopic techniques. PATIENTS AND METHODS: In this prospective study at a British centre, 210 consecutive patients attending for routine colonoscopy were examined for flat or depressed lesions. The examinations were carried out using Japanese techniques by an experienced Japanese endoscopist (T.F.). RESULTS: Overall, 68 adenomas were found, of which 40 (59%) were polypoid, 26 (38%) were flat, and two (3%) appeared depressed. The majority of the adenomas contained areas of mild or moderate dysplasia, but four were severely dysplastic. Two of these were large polypoid tubulovillous adenomas, the third was a 7-mm protruding polyp, and the fourth was a depressed adenoma 6 mm in diameter. Three Dukes' stage A adenocarcinomas were also found. Of these, one was a 20-mm polyp, one a 15-mm flat elevation of the mucosa with a central depression, and the third a 6-mm depression of the mucosa. Finally, four Dukes' B or more advanced adenocarcinomas were found. CONCLUSIONS: The polyp-carcinoma hypothesis prompts colonoscopists to search only for polypoid lesions when screening for malignancy. A significant proportion of early colorectal neoplasms may therefore be missed. European colonoscopists require training in the recognition of flat elevated and depressed lesions in order to detect colorectal malignancies in their early stages.
Granulocyte apheresis in inflammatory bowel disease: possible mechanisms of effect.
We have studied the effects of granulocyte apheresis in 18 patients with ulcerative colitis and 6 with Crohn's disease who had failed to respond to conventional therapy. Patients were treated with weekly apheresis using a granulocyte removal column (GI, Otsuka Pharmaceutical Co., Ltd., London, U.K.). We found a mean reduction in circulating granulocytes of 1.29 x 10(9) cells/L with no significant alterations in red blood cell monocyte, total lymphocyte, absolute T-helper, or T-cytotoxic lymphocyte counts. There were no significant changes in complement levels or immunoglobulin subclasses. There was a significant increase in granulocyte adhesion and a reduction in L-selectin expression. The removal of granulocytes is unlikely to explain the effect of granulocytapheresis. The markedly increased expression of alpha(m) integrin/Mac-1 and low L-selectin expression alter the capability of granulocytes to migrate to sites of inflammation and may be responsible for the improvement observed in patients treated with granulocyte apheresis.
Flat and depressed colorectal neoplasia in England and Japan (Foundation for Promotion of Cancer, Japan and the British Council)
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The role of pethidine in sedation for colonoscopy.
BACKGROUND AND STUDY AIMS: As sedation with a combination of benzodiazepines and opioids has been associated with an increased risk of serious cardiorespiratory events, it is rarely used in upper gastrointestinal endoscopy. The combination is, however, still commonly used in sedation for colonscopy and endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to determine the benefits and disadvantages of adding pethidine to diazepam (Diazemuls) in the sedation for colonoscopic examinations. PATIENTS AND METHODS: Seventy-one consecutive patients attending for routine colonoscopy were randomized in a double-blind, placebo-controlled manner to sedation with Diazemuls alone or Diazemuls with pethidine. The colonoscopist was at liberty to administrate any dose of Diazemuls considered appropriate for the patient's age and size, following which the patient was given an injection of pethidine 50 mg or a placebo. Both the patient and the endoscopist were blind to whether pethidine or a placebo was used. Adequacy of sedation was assessed and oxygen saturation recorded throughout the procedure. Oxygen was administered if the oxygen saturation fell below 92%. Patient satisfaction with sedation and recall of the procedure was recorded, by questionnaire, one day after examination. RESULTS: A total of 71 patients were entered into the trial. The two groups were similar with respect to age, sex, weight, alcohol intake, and state of health. An average of 18 mg of Diazemuls was given in the pethidine group and 19 mg in the placebo group. There was no statistically significant difference in the level of sedation obtained with the two regimens, although there was a tendency for the combination of Diazemuls with pethidine to give deeper sedation. Three patients were inadequately sedated with Diazemuls alone, requiring the code to be broken for pethidine to be given. Nine colonoscopies had to be abandoned due to patient intolerance in the group receiving Diazemuls, compared to five in the group receiving the combination regimen (p = 0.22). Twice as many patients receiving the combination of Diazemuls with pethidine required oxygen supplementation to maintain oxygen saturation during the procedure. This difference was highly statistically significant (p = 0.008). With the administration of supplemental oxygen, the average drop in oxygenation was similar in both groups. Satisfaction with sedation and recall for the procedure were similar in both groups. CONCLUSIONS: Although the patients had no preference for either regime, there may be an advantage in using the combination of Diazemuls and pethidine, as there was a trend for this combination to be preferred by the colonoscopists. The combination of a benzodiazepine with an opiate should be used with caution, however, as there was a greater requirement for oxygen in the group sedated by Diazemuls and pethidine.
Mucosal interleukin-6 secretion in ulcerative colitis. Effects of anti-inflammatory drugs and T-cell stimulation.
BACKGROUND: We have studied modulation of mucosal interleukin-6 (IL-6) secretion by T-cell activation and by anti-inflammatory agents in inflammatory bowel disease. METHODS: In vitro secretion of IL-6 by biopsy specimens from patients with active ulcerative colitis was investigated in the presence of cyclosporin-A (CsA) and drugs that have other anti-inflammatory actions. Biopsy specimens from patients with quiescent ulcerative colitis or controls were stimulated with anti-CD3 antibody to activate mucosal T cells. RESULTS: Stimulation of control specimens increased IL-6 secretion (median increase, 147%; p < 0.003), which was prevented by CsA. In quiescent ulcerative colitis there was enhanced spontaneous secretion of IL-6 but a smaller, non-significant increase after T-cell activation (125%). Dexamethasone inhibited secretion in active ulcerative colitis (p < 0.006). 5-Aminosalicylic acid, 6-mercaptopurine, methotrexate, and indomethacin had no effect. There also tended to be a small reduction with CsA, but this just failed to reach statistical significance. CONCLUSIONS: In quiescent ulcerative colitis the enhanced spontaneous secretion of IL-6 may be a consequence of mucosal T-cell or macrophage activation: the smaller increase after T-cell stimulation suggests that one or both of these two cell types are already pre-activated.