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Colorectal free papers 077–090

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077 THE EFFECT OF ZAPRINAST, A PHOSPHODIESTERASE TYPE 5 INHIBITOR, ON THE SHEEP ISOLATED INTERNAL ANAL SPHINCTER

N. Griffin1, A.G. Acheson1, J.H. Scholefield1, V.G. Wilson2.1Department of Surgery and 2School of Biomedical Sciences, Queen's Medical Centre, Nottingham NG7 2UH, UK

Introduction: Neurogenic relaxation of the internal anal sphincter is mediated by elevation of cyclic GMP, following activation of soluble guanylyl cyclase by nitric oxide. Since the activity of the cyclic nucleotide is also regulated by phosphodiesterase 5, we have examined the effect of zaprinast, an inhibitor of the enzyme, on the sheep isolated internal anal sphincter.

Method: Strips of isolated sheep internal anal sphincter were suspended in 5ml organ baths containing warmed and oxygenated Krebs and isometric tension recordings made. Preparations were exposed to a cumulative concentration of zaprinast (3x10–8M to 3x10–5M), firstly paired with time controls and then in the presence and absence of NG-nitro-L-arginine methyl ester (L-NAME, 100μM), a nitric oxide synthase inhibitor. In a separate series of experiments the effect of sodium nitroprusside, a direct activator of soluble guanylyl cyclase, was examined in the absence and presence of a sub-maximally effective concentration of zaprinast (3x10–6M).

Results: Zaprinast caused a concentration-related relaxation of the sheep anal sphincter with the highest concentration giving a mean effect of 92.3%±2.6 (n=7) compared to 11% ±3.2 loss in tone with time controls over the same period. In the presence of 100 μM L-NAME, the response to higher concentrations of zaprinast was significantly reduced (p<0.05, Student's t-test) but not abolished: 30 μM zaprinast (L-NAME) 72.4%±4.9 (n=7). SNP caused a concentration-related relaxation of the sphincter (EC50 3x10–7M) that was enhanced in the presence of zaprinast ((EC50 1x10–7M) (n=6)).

Conclusion: Zaprinast acts as a PDE 5 inhibitor to relax the sheep internal anal sphincter, however its actions are only partly dependent on the basal release of nitric oxide from the tissue. Further experiments with more selective PDE 5 inhibitors are warranted in order to assess their possible role clinically in conditions related to sphincter hypertonia.

078 SURVEY OF ANO-RECTAL SYMPTOMS AMONGST PATIENTS OBTAINING TOPICAL HAEMORRHOIDAL PREPARATIONS FROM COMMUNITY PHARMACIES

N. Beattie, D. Lamprell, G. Bryson, C. Wilson.Ayr, Prestwick and Troon Local Health Care Co-operative (LHCC) and Department of Surgery, Ayr Hospital, UK

Rectal bleeding is a common symptom amongst the adult population. Whilst most often due to benign ano-rectal disorders, it may be the only symptom of colorectal cancer. The incidence of rectal bleeding amongst people purchasing topical haemorrhoidal preparations (BNF Sections 1.7.1, 1.7.2) over the counter (OTC) from community pharmacies is unknown.

A survey of ano-rectal symptoms was conducted in 20 participating community pharmacies within Ayr, Prestwick and Troon LHCC during February 2001. Sixty-five patients returned completed questionnaires of whom 36 (55%) had filled a prescription (FP10) and 29 (45%) had purchased OTC. Only 8 of the 29 (28%) purchasing OTC had sought the pharmacist's advice. Twenty-eight patients (43%) were over 60 years of age.

Thirty patients (46%) reported rectal bleeding in association with anal symptoms (itch, pain or a lump), 29 (45%) reported anal symptoms with no bleeding and 5 (8%) had rectal bleeding without other symptoms. Four of the five patients with rectal bleeding alone had purchased OTC medications and only one had consulted their GP about their symptoms. Three of these 5 patients might be considered to have “suspicious symptoms” (age >60 years - 2, passing dark blood - 1).

A high incidence of rectal bleeding (54%) was found amongst patients obtaining topical haemorrhoidal preparations (61% of those filling prescriptions vs 45% of those purchasing OTC). The majority of patients (86%) reporting bleeding had associated anal symptoms and were considered low risk for cancer. The majority (69%) reporting bleeding had consulted their GP about their symptoms. A small number reporting bleeding and purchasing OTC topical haemorrhoidal preparations should be consulting their GPs. Community pharmacists need to be aware of the possibility of patients treating themselves inappropriately.

079 ANALYSIS OF SYMPTOMATOLOGY OF PATIENTS PRESENTING TO THE RECTAL BLEEDING CLINIC: NEED FOR BETTER REFERRAL GUIDELINES

A.B. Harikrishnan, M. Bassuini, A.J. Watkins1, A.R. Morgan, N.D. Carr, J. Beynon.Department of Coloproctology, Singleton Hospital, Swansea SA2 8QA, UK; 1University of Wales, Swansea SA2 8PP, UK

Introduction: Rectal bleeding clinics (RBC) act as the pick-up point for colorectal cancers ideally in their early stages. Referral guidelines for RBC vary and are yet to be formalised on a national scale. Appropriate referral guidelines will facilitate patient selection for RBCs.

Methods and Results: 2597 patients were seen in the RBC over a six-year period between October 1994 and September 2000. Patients were referred by their general practitioners. All patients had a detailed history, clinical exam and flexible sigmoidoscopy (FS). 123(5%) patients were diagnosed as having colorectal cancer (mean age 70, range 45 – 90). 390(15%) patients had polyps (mean age 62, range 19 – 94) and were referred for formal colonoscopy. A total of 15 symptoms were recorded in these patients and analysed in separate groups (cancer, polyp, sex and age). The incidence of change in bowel habit (CIBH), loose stool (LS), mucous discharge (MD), blood mixed with stool (BS), weight loss, palpable abdominal mass and mass palpable per rectum were significantly (p < 0.05) increased in the cancer group. Further, in the cancer group, symptoms of CIBH, LS, MD and BS were significantly (p < 0.05) present in patients over 70 years. Interestingly, abdominal pain, constipation and fresh bleeding per rectum were not significantly associated with the diagnosis of malignancy or polyps.

Discussion and Conclusion: This study demonstrates and is in agreement with other studies that the symptomatology of colorectal cancer is quite distinct and should be incorporated into the RBC referral guidelines. In this series only 5% of the referred patients had colorectal cancer and 15% had polyps. More stringent RBC referral guidelines based on these symptoms and related to age would aid in selection of patients for rectal bleeding clinics.

080 A DOUBLE-BLIND, PLACEBO CONTROLLED PILOT STUDY TO ASSESS THE EFFECTS OF A PROBIOTIC ON THE RESPONSE OF THE INTESTINAL MICROFLORA TO HELICOBACTER PYLORI ERADICATION THERAPY

J.A.J. Madden1, S. Plummer2, N.T. Plummer2, M. Herbison1, J.O. Hunter1.1Department of Gastroenterology, Addenbrooke's NHS Trust, Cambridge CB2 2QQ; 2Cultech Ltd, York Chambers, York St, Swansea SA1 3NJ, UK

Introduction: Antibiotic therapy can detrimentally alter the intestinal microflora. Probiotics are preparations of non-pathogenic intestinal bacteria which may be beneficial to human health. The effects of supplementation with Bifidobacterium longum and Lactobacillus acidophilus (HLC: Cultech Ltd, Port Talbot, UK) has been studied in patients undergoing eradication of Helicobacter pylori by antibiotics.

Methods: 30 patients positive for H. pylori serology were recruited into the trial (8 were excluded for non-compliance). Patients were randomised into three treatment groups: antibiotics days 1–7 [metronidazole 400mg tds, amoxycillin 500mg qds, lansoprazole 30mg bd], with placebo days 1–15 (n=9), or the same antibiotics days 1–7 with probiotics days 1–15 (n=7), or the antibiotics with placebo days 1–7 and with probiotics days 8–15 (n=6). Patients provided stool samples on days 1, 7, 12, 17 & 27. Specimens were analysed using standard microbiological techniques.

Results: Administration of antibiotics alone resulted in a significant increase in numbers of aerobes between days 1 and 7 (p=0.001). When probiotics were given after antibiotics, numbers of aerobes fell significantly between days 7 and 27 (p=0.021), a change not observed with antibiotics alone. When antibiotics were supplemented with probiotics, there was a decrease in the numbers of enterobacteriaceae between days 1 and 7 (p=0.068); these organisms were below limits of detection at day 27. There were no differences between levels of lactic acid bacteria between the three groups.

Conclusions: Probiotic supplementation may be able to prevent some of the alterations to the intestinal microflora resulting from broad-spectrum antibiotic therapy. This may be of importance in the prevention of antibiotic-related diseases.

081 A COMPARATIVE STUDY ON THE QUALITY OF LIFE IN PATIENTS WITH ILEOSTOMY VERSUS COLOSTOMY

M.A. Silva, G. Ratnayake, K.I. Deen.University Surgical Unit, Teaching Hospital of North Colombo, Ragama, Sri Lanka

Background: The choice of an ileostomy as the preferred option for proximal diversion over colostomy, has been a recent topic of interest. This study evaluated the quality of life of patients with an ileostomy and compared it with that of patients with a colostomy.

Methods: Life quality of 25 patients with an ileostomy (median age 42 years, range 22–76 years) was compared with 25 patients with a colostomy (median age 44 years, range 18–70 years). A self administered structured questionnaire was used with responses obtained for ten life quality questions on visual analogue rating scale (0–100mm) and graded good (71–100), satisfactory (31–70) or poor (0–30).

Results: Purchase of the stoma appliance was without much difficulty in 22 (88%) patients with an ileostomy compared with 16 (64%) patients with a colostomy (P=0.09:x2:NS). Effluent was tolerable in 18 (72%) patients with an ileostomy as compared with only 7 (28%) patients with a colostomy (P=0.002:x2). Appetite was not significantly affected in all patients with an ileostomy (100%), compared with 64% of patients with a colostomy (P=0.002:x2), travel by public transport was not affected in 32% of patients with ileostomy cf 28% with colostomy (NS), dress in 20% of patients with an ileostomy cf 24% with colostomy (NS) and daily activities 28% of patients with an ileostomy cf 24% with colostomy (NS). Furthermore, 68% with an ileostomy did not have a problem with personal hygiene, compared with 40% with a colostomy (NS), while 95% with an ileostomy abstained from sexual activity compared with 81% with a colostomy (NS).

Conclusion: Both ileostomy and colostomy resulted in significant impairment of quality of life in patients. However, with an ileostomy, the effluent was more tolerable, had less of an impact on personal hygiene and preserved appetite compared with patients with a colostomy. There were no differences in appetite, travel, dress, daily chores and sexual activity between the two groups.

082 ADENOMA PREVALENCE AND ILEAL MUCOSA IN POUCH VS NEOTERMINAL ILEUM

C.J. Groves, I.G. Beveridge, D.J. Swain, I.C. Talbot, A.B. Price, R.K. Phillips.

Introduction: The recent findings of adenomas of ileal origin in up to 42% of FAP pouches has caused some concern as to the subsequent long-term risk of ileal pouch cancers. The development of ileal adenomas in FAP may be a phenomenon restricted to the pouch, occurring as a result of environmental changes. We aimed to describe polyp burden and determine the characteristics of FAP pouch/ neo-terminal ileal mucosa.

Methods: A video-flexible sigmoidoscope was used to compare the ileal mucosa within the pouch to 20cm of neo-terminal ileum proximal to the pouch in 32 consecutive FAP patients (18M, 14F, median age 37, IQR 31–44). The number and size of polyps were counted and 4 polyp biopsies/ 4 normal biopsies were taken from each area. Biopsies were examined for presence of adenoma and were also scored for acute and chronic pouchitis by an experienced pathologist using the Moskovitz criteria.

Results: Adenomatous polyps were seen and confirmed by biopsy in 17/32 (53%) pouches compared to just 1/32 (3%) adenomatous polyps in the neo-terminal ileum of the same patients. The median number of pouch adenomas was 4 (range 1–50) and median size was 3mm (range 1–40mm). 12 patients (75%) had tubular adenomas with mild dysplasia and 5 patients (25%) had adenomas with either villous or tubulovillous architecture or moderate dysplasia. There was no severe dysplasia and there were no cancers. Acute pouchitis (median score 1, range 1–5) was found in 5/32 (16%) patients and chronic pouchitis (median score 2, range 1–4) in 18/32 (56%). Chronic pouchitis, score 4, was found in the neo-terminal ileum of 1/32 (3%) patients but in all other cases the neo-terminal ileal mucosa was normal. The presence of pouchitis did not predict presence of adenomas which occurred in 9/17(53%) patients with, compared to 8/15(53%) without pouchitis.

Conclusion: The development of ileal adenomas in patients with FAP is almost exclusively restricted to the pouch, with the spectrum of severity being similar to that seen in the duodenum of FAP patients. Mild pouchitis occurs, but is not predictive of adenoma formation.

083 RESULTS OF NON STIMULATED GRACILIS MUSCLE TRANSPOSITION FOR RESTORATION OF ANAL CONTINENCE

L.S.S. Ranatunga, G. Ratnayaka, K.I. Deen.Professorial Surgical Unit, University of Kelaniya, Sri Lanka

Background: Stimulated gracilis muscle transposition is now widely practised. However, it is expensive and is also associated with a high postoperative complication rate. Our aim was to assess the efficacy of non-stimulated gracilis transposition and to compare the outcome with a published series of stimulated graciloplasty.

Method: Between November 1997 and May 2000 13 patients (11 male; median age 22 years; range 11 to 40) underwent 15 gracilis transpositions (2 bilateral) without vascular delay. The Cleveland Continence Score (0–20), Maximum Resting Pressure (MRP) and Maximum Squeeze Pressure (MSP) were assessed before and after operation. Follow up was for a median (range) of 12 months (6 to 36 months).

Results: There were 3 (20%) complications [wound infection-2; fistula-1]. There were no complications associated with stoma closure. There was a significant improvement in continence score [Preop; median (range) – 20 (19–20) vs Postop: 11(7–12) – P< 0.001 Wilcoxon Rank Sum Test] Significant improvement was also seen in MRP and MSP after operation. [Median MRP; Preop vs Postop – 10 mm Hg vs 29 mm Hg – P< 0.007 and Median MSP; Preop vs Postop – 18.1 mm Hg vs 62 mm Hg – P<0.005 – Wilcoxon Rank Sum test]. Compared with a collected series of stimulated graciloplasty, non-stimulated gracilis transposition showed a comparable improvement in continence scores and anal manometry but revealed a lower overall complication rate. (20% vs 57%; Non-stimulated vs Stimulated).

Conclusion: Gracilis transposition without stimulation is cost effective, associated with low postoperative morbidity and results in significant improvement in continence.

084 FUNCTIONAL OUTCOME OF RECTOPEXY FOR OBSTRUCTIVE DEFAECATION: WHAT DO THE PATIENTS THINK?

T.V. Chandra Sekaran, A.B. Harikrishnan, A.R. Morgan, J. Beynon, N.D. Carr.Department of Coloproctology, Singleton Hospital, Swansea, UK

Introduction: Obstructive defaecation (OD) is characterised by prolonged straining at stools and a sense of incomplete emptying. This may be secondary to intra-rectal intussusception and rectopexy has been used to correct this abnormality in attempt to improve OD. The aim of this study is to assess patient's perspective of the functional outcome of rectopexy.

Methods: Thirty-six patients (male 2; female 34, median age 54years, range 20–71) who underwent rectopexy for OD were identified. Their symptoms before and after operation were analysed. A simple functional assessment questionnaire was sent to 35 patients by post. Twenty-seven patients (77%) responded.

Results: Symptoms of prolonged straining and incomplete evacuation improved in 40% of patients while 25% had no change noticeable and another 25% had worsening of these symptoms after operation. Vaginal and rectal digitation resolved in only 10% of patients whereas 30% reported some improvement, 40% no change and 20 % were worse after rectopexy. Ten patients (37%) were satisfied with the outcome of surgery. Five patients (19%) would recommend a rectopexy to someone with similar symptoms, while 10 (37%) would not and the rest (44%) were unsure.

Conclusion: Persisting or worsening of symptoms was observed in a quarter of patients after rectopexy for OD. The overall patient satisfaction following rectopexy for OD is less than ideal. Hence careful patient selection and counselling prior to surgery is essential.

085 MAGNETIC RESONANCE IMAGING IN THE ROUTINE FOLLOW-UP OF COLORECTAL CANCER PATIENTS

L. Titu, D.J. Breen1, J. Hartley, A.A. Nicholson1, P.J. Drew, J.R.T. Monson.Academic Surgical Unit, University of Hull; 1Centre for Magnetic Resonance Investigations, Hull Royal Infirmary, Hull, UK

Background: Traditional policies for follow-up of colorectal cancer patients after curative surgery often detect recurrent disease at a stage in which palliation is the only option. We proposed to determine if a protocol of routine scanning by Magnetic Resonance Imaging (MRI) improves the detection of resectable recurrent colorectal cancer.

Methods: A cohort of colorectal cancer patients, who underwent curative surgery between 1995 and 1999, were included in a follow-up programme employing routine MRI scans at 3–6 months intervals, in addition to established clinical, biochemical and endoscopic tests. For patients with rectal and left-sided colonic tumours both the liver and pelvis were imaged, whereas patients with right-sided colon cancers underwent liver surveillance only. Cases were analysed for the impact of MRI on the detection of resectable recurrent disease and survival rates.

Results: Of the 278 patients who underwent MRI liver surveillance, 34 (12%) developed liver metastases over a mean follow-up period of 20 months (inter-quartile range 12–26). MRI detected liver metastases with 88% sensitivity and 90% specificity. Hepatic metastases were diagnosed solely by MRI in 14 cases (48%). Only 5 patients (15%) were eligible for hepatic resection and are alive 32–45 months after surgery. All cases unsuitable for surgery died with a median survival time of 10.5 months after diagnosis (IQ range 5–17.5). Pelvic recurrence was observed in 29 (13%) of the 217 patients who underwent regular pelvis MRI examination over a median period of 21 months (inter-quartile range 12–27) follow-up. Recurrent pelvic disease was picked up by MRI with 83% sensitivity and 84% specificity. In 8 patients (27%) with pelvic disease MRI was the sole positive test. Surgery with curative intent was possible in only 5 cases (21%). None of the patients with local recurrence was alive after a median period of 9 months (IQ range 6–22) follow-up.

Conclusions: Routine follow-up by MRI can contribute to the detection of resectable liver metastases but has little impact on the diagnosis of recurrent pelvic disease at a stage when curative therapy can be successfully undertaken.

086 CONTRAST RADIOLOGY, COMPUTED TOMOGRAPHY (CT) AND ULTRASONOGRAPHY (US) IN DETECTING SEPTIC ABDOMINAL COMPLICATIONS OF CROHN'S DISEASE (CD)

G. Maconi, F. Parente, G. Sampietro, A. Russo, S. Ardizzone, M. Cristaldi, G. Pompili, M. Molteni, A.M. Taschieri, G. Bianchi Porro.Department of Gastroenterology, Radiology and Surgery; L. Sacco University Hospital, Milan, Italy; Epidemiology Unit, Local Health Authority, Milan, Italy

Background: The accuracy of radiographic and ultrasonographic evaluation of septic complications of CD is still debated.

Aim: To determine the accuracy of US and contrast radiography in detecting intestinal fistulae and abscesses complicating CD in patients undergoing surgery.

Methods: In this prospective study the results of US, barium radiology and CT in were compared with intraoperative findings in 128 consecutive patients operated upon immediately after complete evaluation of the intestinal tract by colonoscopy and double contrast barium enema, small bowel enteroclysis and abdominal US, as well as CT in patients with clinically suspected septic complications. Results were analysed on a per-patient basis.

Results: Internal fistulae and abscesses were identified intraoperatively in 56 (43.7%) and 26 (20.3%) pts. Diagnostic accuracy of US and x-ray studies in detecting internal fistulae was comparable (85.2% vs 84.8%) with sensitivity of 71.4% and 69.6%, and specificity of 95.8% for both. The combination of US and radiography increased the sensitivity in diagnosing this complication to 90%. Sensitivity in detecting entero-enteric fistulae was significantly lower than for entero-mesenteric fistulae for both x-ray and US studies but no difference was found between US and x-ray. The accuracy of US, barium studies and CT was 88.5%, 80.3%, and 77%, respectively. Presence of abscesses was correctly detected in 90.9% of cases by US and in 86.4% by CT, although accuracy was slightly higher for CT (91.8 %) than for US (86.9%).

Conclusion: Although barium radiology is widely considered the method of choice in detection of internal fistulae, its accuracy is not entirely satisfactory. US and CT showed comparable accuracy. Only US, in more severe CD, or the combination of US and barium studies can reliably detect most internal fistulae.

087 CYCLOOXYGENASE-2 EXPRESSION AND DYSPLASIA IN HUMAN COLORECTAL ADENOMATOUS POLYPS

K.M. Sheehan1, F. O'Connell1, A. O'Grady1, M.F. Byrne2, M.B. Leader1, E.W. Kay1, F.E. Murray2.1Department of Pathology, Beaumont Hospital and Royal College of Surgeons in Ireland; 2Department of Gastroenterology and Clinical Pharmacology, Beaumont Hospital, Dublin, Ireland

Introduction: Cyclooxygenase-2 (COX-2) is a target of aspirin and other non-steroidal anti-inflammatory drugs and is implicated in the pathogenesis of colorectal cancer. The objective of this study was to evaluate the extent of COX-2 in pre-malignant colorectal polyps and to assess the relationship between COX-2 and the level of dysplasia in these lesions.

Methods: Whole polypectomy specimens were retrieved by endoscopic or surgical resection. Following formalin fixation and paraffin embedding, the polyps were histologically evaluated for size, type and grade of dysplasia. The extent of COX-2 expression was measured by avidin biotin immunohistochemical technique using a monoclonal COX-2 antibody. The extent of COX-2 expression was graded according to percentage epithelial COX-2 expression.

Results: Polyps were retrieved from 109 patients (72 males). The mean age was 65years (range 33–85). The polyps were of the following histological type: 10 hyperplastic, 35 tubular adenomas, 55 tubulovillous adenomas and 9 villous adenomas. Nineteen showed mild dysplasia, 63 moderate dysplasia and 17 focal or severe dysplasia (including 2 with focal invasion). The average polyp size was 1.24cms (range 0.2–6.0cms). Nine hyperplastic polyps were COX-2 negative and 1 was positive (This patient had a co-existing adenocarcinoma elsewhere in the colon). In 8% of the adenomas, adjacent normal colon weakly expressed COX-2. COX-2 expression was more extensive in larger polyps (p=0.01) and in those with a higher villous component. Polyps with mild dysplasia expressed COX-2 in 35% of the epithelial cells whereas severely dysplastic polyps expressed COX-2 in 60% of the cells (p=0.03). Within a polyp, there was a corresponding increase in COX-2 expression within epithelium showing higher grade of dysplasia.

Conclusion: COX-2 is directly related to polyp size and grade of dysplasia in colorectal polyps. This suggests that the role of COX-2 in colorectal cancer may be at an early stage in the adenoma-carcinoma sequence and non-steroidal anti-inflammatory drugs may be useful chemopreventative agents for this disease.

088 FLAT AND DEPRESSED NEOPLASMS: MATCHED PAIR STUDY BETWEEN A UK AND A JAPANESE POPULATION

N. Suzuki1,2, B.P. Saunders1, M.D. Rutter1, S. Thomas-Gibson1, C.B. Williams1, K. Ichikawa2, T. Matsumoto2, T. Arakawa2.1Wolfson Unit for Endoscopy, St Mark's Hospital, London, UK; 2Dept Endoscopy, Osaka City University Hospital, Japan

Background: Flat and depressed colorectal neoplasms may have more malignant potential than polypoid lesions, and may occur more frequently in Japan than in Western countries. As differing definitions are used, the incidence of these lesions is ill-defined. We examined the proportion of such lesions detected in UK & Japan in patients undergoing colonoscopy performed by a single colonoscopist.

Methods: 164 patients found to have polyps on colonoscopy at St. Mark's Hospital, UK (SMH) were age and sex-matched with 164 patients who had previously had polyps detected by the same colonoscopist (NS) at Osaka City University Hospital, Japan (OCU). FAP, HNPCC and IBD patients were excluded. Polyp characteristics (shape, location, size and histology) were documented.

Results: 255 polyps were confirmed histologically in the 164 SMH patients, compared with 260 in the 164 OCU patients (see table). Of the 43 flat & 3 depressed lesions in SMH, no severely dysplastic or cancerous lesions were seen; whereas of the 35 flat & 6 depressed lesions in OCU, 10 (24%) showed severe dysplasia (9) or invasive cancer (1).

Abstract 088

Conclusion: (1) There was no significant difference in the proportion of flat & depressed neoplasms detected in UK & Japan when the colonoscopy was performed by the same endoscopist using the same definition. (2) The difference in rate of malignancy on these lesions needs to be further investigated.

089 THE INFLUENCE OF ANTIBIOTICS ON IRRITABLE BOWEL SYNDROME: A RANDOMISED CONTROLLED TRIAL

P. Moayyedi1, S. Duffett, S. Mason2, J. Brown2, A.T.R. Axon.1City Hospital, Dudley Road, Birmingham. Centre for Digestive Diseases, Leeds General Infirmary, Great George Street, Leeds; 2NYCTRU, University of Leeds, UK

Introduction: Observational studies have suggested that irritable bowel syndrome (IBS) occurs after infective gastroenteritis and antibiotic prescription. This suggests alteration of the intestinal bacterial flora may be involved in the pathogenesis of IBS. Observational studies, however, are difficult to interpret as results could be due to confounding factors or bias. We therefore evaluated this hypothesis in a randomised double blind placebo controlled trial.

Methods: This trial represents a secondary outcome from a trial of H. pylori screening and treatment in the community. Subjects between the ages of 40–49 years were invited to attend their local general practice. H. pylori infection was assessed by 13C-urea breath test and positive individuals were randomised to omeprazole 20 mg bd, clarithromycin 250 mg bd and tinidazole 500 mg bd for one week or identical placebos. Randomisation was performed at a central clinical trials unit using computer generated random numbers. A research nurse interviewed subjects with an IBS questionnaire at baseline, 6 months and two years. Participants were defined as having IBS if three or more Manning's criteria were present.

Results: 1,713/2329 (74%) participants attended at two years with complete questionnaires. 1,439 subjects did not have IBS at baseline and at two years IBS was present in 63/721 (9%) receiving placebo and 41/718 (6%) allocated antibiotics (odds ratio for those taking antibiotics = 0.63; 95% CI = 0.42 to 0.95; p=0.03). Evaluating individual IBS symptoms suggested frequent stool (OR = 0.55; 95% CI = 0.3 to 1.0; p = 0.03) and loose stool (OR = 0.43; 95% CI = 0.2 to 0.7; p = 0.002) were significantly less frequent in subjects given antibiotics. 274 participants had IBS at baseline. At two years 54/129 (42%) of the placebo group and 61/145 (42%) of the antibiotic group still had IBS (OR = 1.0; 95% CI = 0.6 to 1.6; p=1.00).

Conclusion: This randomised controlled trial does not support the hypothesis that clarithromycin and tinidazole exacerbates IBS. Indeed, in those subjects without IBS at baseline, antibiotic prescription appears to be protective.

090 IS THE P53-APOPTOTIC PATHWAY SIGNIFICANT IN THE SHORT COURSE RADIOTHERAPY?

H. Ishikawa1,2, I.C. Talbot2.1First Department. of Surgery, Nara Medical University, Kashihara, Japan; 2Academic Department of Pathology & ICRF, St Mark's Hospital, Harrow, UK

Aim: Selection of patients who will benefit from preoperative adjuvant radiotherapy for operable rectal cancer remains problem. p53 is believed to play a significant role in apoptosis after radiation. Concentrating on short course radiotherapy, we have examined relationship between apoptotic cell death, proliferative activity, and the expression of apoptosis-regulating proteins.

Methods: 26 patients underwent operation from June 1982 to October 1984 after short course radiotherapy (15Gy). Patients' aged was between 27 and 77 years (median 57), 11 were male. Tumours stages were (Dukes) A (2), B (11), C (13). Sections of paired biopsies and post-irradiated surgical specimens of each tumours were immunohistochemically stained for p53, Bcl-2, BCL-XL, Bax, Ki67, & P21/WAF1. The proliferative index (PI) was the percentage of cells positive for Ki67. The TUNEL method was used to identify apoptotic cells, the apoptotic index (AI) being the percentage of positive tumour cells.

Results: After radiotherapy, the average AI increased significantly increased (2.2 v.s 7.5 ; p<0.01). In contrast, the proliferative activity (PI) decreased slightly (48.3 v.s 42.7; p>0.05). Bax immuno-staining was in 3/26(11.5%) of biopsies and in 15/26 (57.7% ) of surgical specimens. Regarding other proteins, there were no significant differences between paired specimens. In surgical specimens, tumours with low expression for p53 (p53-L) exhibited a high AI and a low PI, in contrast with those with p53-H. Combination of p53 and p21/ WAF1 revealed a subgroup p53(L) / p21/WAF1(+) with the highest AI (10.3) and the lowest PI (30.4) of all other subgroups. Considering Bcl-2 /Bax balance, tumours with Bcl-2 (-) / Bax (H) also showed a high AI (9.7) and the lowest PI (28.5). In contrary, Bcl-Xl(L) in the p53 (L) was associated with the highest PI (59.0).

Conclusion: Apoptotic cell death and up-regulation of Bax protein were induced by radiation in vivo. These results confirm a previously suspected important local effect of the p53-apoptotic pathway after short course preoperative radiotherapy.

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