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209 FREQUENCY OF STOOL EXAMINATION: EFFECT ON REPORTED RECTAL BLEEDING
K.K. Sundaram, E. Rink, I. Hartley, J.Y. Kang.St George's Hospital and St George's Hospital Medical School, London, UK
Background: Rectal bleeding is an important symptom of colorectal cancer. However, up to 45% of people seldom examine their stools: these individuals may be less likely to report rectal bleeding. This phenomenon has not to date been studied formally.
Aims: To determine (1) the proportion of community subjects who examine their stools or toilet paper at different frequencies, (2) whether the incidence of reported rectal bleeding is related to frequency of inspection. Methods: A questionnaire was developed, validated and sent by post to subjects selected at random from patient lists of 4 general practices in south west London. Equal numbers were selected within 5 year age bands between 50 and 79 years, and between sexes. Reminders were sent to non responders after 4 and then 8 weeks.
Results: 2073 subjects were included in the study. 1633 (79%) completed the questionnaire, 162 (8%) subjects declined, and 278 (13%) did not respond. The cumulative proportion of individuals who examined their stools and toilet paper at various frequencies were: every time – 31%,45%; more than once a week - 67%,74%; more than once a month – 80%,84%. 12% and 9% respectively never examine their stools or toilet paper. Men examined more frequently than women. Age had no effect. 102/439 (22%) of individuals who always examined their stools or toilet paper had noticed rectal bleeding in the past year, compared to only 4/100 (4%) of subjects who never examined either, p< 0.001. 149/429 (35%) of individuals who examined their stools or paper every time had a history of piles compared to 21/101 (21%) of individuals who never checked, p < 0.006.
Discussion: Many individuals do not examine their stool or toilet paper regularly. 9% never examine either. Infrequent examiners reported rectal bleeding less often than those who examined regularly, and this behaviour may potentially delay the presentation of colorectal cancer. It would be important to determine whether colorectal cancer patients who regularly check for bleeding present at an earlier stage than those who examine infrequently, since public education may then be a potential way of improving outcome.
210 TREATMENT OF FAECAL INCONTINENCE DUE TO SYSTEMIC SCLEROSIS WITH SACRAL NERVE STIMULATION
N.J. Kenefick, C.J. Vaizey, R.J. Nicholls, R. Cohen, M.A. Kamm.St Mark's Hospital, London, UK
Introduction: Faecal incontinence occurs in over a third of patients with systemic sclerosis. Aetiological factors include internal anal sphincter fibrosis, rectal wall fibrosis, small bowel involvement and an autonomic neuropathy. Sacral nerve stimulation is a novel treatment for faecal incontinence that is effective where other treatments have failed. Its value in systemic sclerosis has therefore been evaluated.
Patients and Methods: Five women, median age 61 years (range 30–71), with faecal incontinence secondary to scleroderma were treated with initial temporary, and subsequent permanent stimulation. The median pre-operative episodes of faecal incontinence per week was 15 (7–25). The median pre-operative duration of incontinence was 5 years (5–9) and of scleroderma 13 years (4–29). All had failed traditional treatment including anti-diarrhoeal agents and behavioural therapy (biofeedback). A three-week bowel habit diary, quality of life assessment (SF36), endoanal ultrasound and anorectal physiological testing were performed.
Results: At median follow up of 24 months (range 6–60) four patients were continent, one had failed temporary stimulation. On diary the episodes of faecal incontinence per week decreased from 15, 11, 23 and 7 to 0 in all patients. Urgency and urge incontinence resolved in all patients with the median ability to defer improving from <1-minute (0–1) pre to 12.5 mins (5–15) post stimulation. Adjusted scores for the SF-36 quality of life questionnaire showed an overall improvement. The internal anal sphincter was atrophic in all patients, median width 1.0 mm (0–1.6mm; normal range 2.4–3.4mm). Anorectal physiological testing showed an increase in resting pressure (37 (10) mm H2O (median (SD)) pre v 65 (16) post) and squeeze pressure (89 (48) pre v 105 (67) post). Rectal sensation to distension improved at threshold volume (53 (17) ml air v 33 (20)), urge volume (83 (18) v 58 (25)) and maximum tolerated volume (143 (23) v 75 (34)). There were no major complications.
Conclusion: Sacral nerve stimulation is a safe and very effective treatment for faecal incontinence in patients suffering with scleroderma when other treatments have failed.
211 PAIN COPING STRATEGIES AND QUALITY OF LIFE IN PATIENTS WITH CHRONIC ANAL FISSURE
N. Griffin1, A.G. Acheson1, C. Sheard2, C. Glazebrook2, J.H. Scholefield1.Departments of1Surgery and2Behavioural Sciences, Queens Medical Centre, Nottingham NG7 2UH, UK
Introduction: To date, there has been little evaluation into the quality of life of patients with chronic anal fissure. This is a prospective study assessing physical and mental health of fissure patients prior to and following topical treatment; pain coping strategies are also identified to see if these affect outcome.
Methods: New patients attending the fissure clinic were recruited prospectively into the study over a 2 month period. Patients were initially given 3 questionnaires to complete: 1) the Short-Form 36 Health Survey (SF36), 2) the Pain Coping Strategies Questionnaire and 3) a general questionnaire recording patients' demographic details and symptoms on a visual analogue scale (VAS). Following an 8 week course of topical treatment, patients repeated the SF36 and symptoms were again recorded on a VAS. Healing of fissure was noted.
Results: 23 patients entered the study; 8 male, 15 female with mean age 39 years (range 17–80). Median duration of fissure was 9 months (1.5 months – 10 years). Before treatment, median VAS for pain, bleeding and irritation were 6, 1 and 5. On the SF 36, patients scored below normal values for all scales except role emotional functioning and mental health. Fissure patients had more pain than age and sex matched normal population (p=0.00, Wilcoxon). Gender did not affect any of the SF 36 sub-scales. Duration of fissure positively correlated with role physical functioning and role emotional functioning (p<0.05). On follow-up, healing was complete in 15 patients (65%). Symptoms were significantly reduced in this group. Repeating the SF36 showed an improvement in role-physical functioning (p<0.05). Ignoring sensations was an adaptive pain coping strategy, being employed more often in the group responding to treatment (p=<0.05).
Conclusion: Successful treatment of chronic anal fissure leads to symptomatic improvement and beneficially affects role physical functioning. Patients' coping strategies appear to have an influence on outcome, with ignoring sensations being a good predictor of response.
212 COLONIC DIVERTICULITIS: A DISEASE ON THE RISE?
S. Subramanian1, A. Tinto2, A. Majeed3, D.M. Melville4, A.R. Hart5, C.R. Morris5, J.D. Maxwell1, J.Y. Kang1Departments of1Gastroenterology and4Surgery, St George's Hospital, London;2Office for National Statistics, London;3University College London; School of Medicine, University of East Anglia5, Norwich, UK
Background: Little data exist on time trends for colonic diverticulitis. We studied hospital admission data for the whole of England from 1989/1990 to 1999/2000.
Materials and Methods: Admission rates for colonic diverticulitis (ICD9: 562.1, ICD10: K57.2–57.9), excluding day cases but including diverticular abscess and perforation, operation and case fatality rates were obtained from Department of Health Hospital Episode Statistics.
Results: There has been a steady increase in age-standardised hospital admission rates for both sexes and in all age groups over the study period. Admission rates increased with age for both sexes. The percentage of hospital admissions with an operation has also risen for both males and females. There has been no significant change in case fatality rates over this time for either sex (see table⇓).
Conclusions: The hospital admission rates for colonic diverticulitis has increased from 1989/90 to 1999/00. As the proportion of patients who had surgical operations has also increased, while case fatality rates have remained much the same, the rise in admission rates may be due to a true increase in the incidence of colonic diverticulitis. With an aging population, colonic diverticulitis is likely be an increasing health problem in England.
213 THE RELATIONSHIP BETWEEN CYCLOOXYGENASE-2 EXPRESSION AND MICROVESSEL DENSITY IN COLORECTAL CANCER
C. Steele1, K.M. Sheehan2, R. Cummins2, A. O'Grady2, K. Sheahan4, D.P. O'Donoghue5, D.J. Fitzgerald3, E.W. Kay2, F.E. Murray1,3.1Gastrointestinal Unit and2Department of Pathology, Beaumont Hospital Dublin;3Department of Clinical Pharmacology, Royal College of Surgeons, Dublin;4Departments of Pathology and Gastroenterology, St Vincent's Hospital, Dublin, Ireland
Introduction: Cyclooxygenase 2 (COX-2) is up regulated in colorectal carcinoma and is related to survival, lymph node and distant metastases. The exact role of COX-2 in colorectal cancer, in particular with regard to angiogenesis and tumour vascular development, is yet to be delineated. Our group have shown that VEGF mediates endothelial cell proliferation via COX and that adhesion of endothelial cells to the extracellular matrix via integrins induces COX-2. The aim of this study was to examine the relationship between tumour cell expression of COX-2 and vessel formation within tumour by microvessel density (MVD) in colorectal cancer.
Methods: Seventy patients for whom full clinical and pathological data were available from our database were selected retrospectively for analysis. Paraffin embedded tissue from archival primary tumour material was analysed by immunhistochemical methods for COX-2 and MVD. COX-2 polyclonal human antibody (Cayman) and an endothelial cell antibody, CD-34 (clone QBEND-10, Dako) were used on serial sections using the avidin biotin method. COX-2 was graded by percentage of epithelial cell staining and intensity. MVD was calculated by mean vessel count of five high power fields (x 200) per slide in tumour involved area. Two blinded observers performed both analyses.
Results: Of the 70 cases, 2 were Dukes' stage A, 26 were stage B, 29 were stage C and 13 were stage D. COX-2 was present in almost 90% of cases. COX-2 staining was present in tumour epithelial cells, inflammatory cells, fibroblasts and endothelial cells. There was variation in staining intensity between tumours. Correlation analysis was performed between intensity of COX-2 expression and MVD. No significant correlation was found between these two groups (r= -0.075). No correlation was found between Dukes stage overall or between individual Dukes' stage and MVD. (Dukes' B=0.105, Dukes' C=0.012, Dukes' D=-0.189).
Conclusion: This study demonstrates no association between microvessel density and either the intensity of COX-2 expression in tumour cells or Dukes' stage. These findings suggest that COX-2 expression does not play a role in determining augmented neovascularisation associated with colorectal cancer. This is in keeping with recent evidence that it is the host COX-2 and COX-1 that are important in angiogenesis.
214 CYTOKERATIN IMMUNOREACTIVITY IN BENIGN PERICOLIC LYMPH NODES: AN IMMUNOHISTOCHEMICAL STUDY OF 101 LYMPH NODES
V.I. Shah1, P.J. Arumugam1, J. Beynon1.1Singleton Hospital, Swansea, Wales, UK
Background: Several studies have demonstrated scattered single cytokeratin immunoreactive cells in morphologically benign regional draining lymph nodes from cases of Dukes B colorectal cancer. In most studies their presence correlated poorly with tumor recurrence and survival. It is not clear whether these cells represent native cells of the lymph node or occult micrometastasis.
Design: Formalin-fixed paraffin-embedded sections from 101 histologically benign lymph nodes from 38 patients who had undergone colorectal resections for benign conditions [diverticular disease (18), inflammatory bowel disease (11), slow transit constipation (6), volvulus (1), ischaemia (1), angiodysplasia (1)] and had no history of malignancy at the time of sugery or during a mean follow up period of atleast 30 months were immunostained with AE1/AE3 (DAKO, monoclonal,1:100, 30 min, protease 1 pretreatment, 12 min), Cam 5.2 (Becton-Dickinson, monoclonal,1:20, 30 min, protease 1 pretreatment, 8 min) and pan-cytokeratin (DAKO, MNF116, 1:100, 30 min, protease 1 pretreatment, 12 min) on a NEXES autostainer using a Ventana detection system. The morphology of the immunoreactive cells was evaluated and their number scored as 0:absent, rare:<1%, 1+:1–5%, 2+:6–10%, 3+:>10%.
Results: A single cytokeratin positive epithelioid cell was identified in 1 (1%) of the lymph nodes in the levels immunostained with AE1/AE3 and Cam 5.2. This cell could not be identified in the level stained with pan-cytokeratin. No cytokeratin positive epithelioid cell was present in any of the other lymph nodes with all 3 antibodies. Rare to 2+ cytokeratin immunoreactive dendritic histiocytes were observed in 50% of lymph nodes with MNF 119 and in 14% with Cam 5.2. With AE1/AE3, no immunoreactive dendritic histiocytes were seen in any of the cases.
Conclusion: Isolated cytokeratin positive epithelioid cells are rare in benign pericolic lymph nodes. Cytokeratin positive epithelioid cells in lymph nodes draining a carcinoma could represent either tumor cells or histiocytic cells which have adsorbed cytokeratin antigen shed by tumor cells. AE1/AE3 is more specific than Cam 5.2 and pan-cytokeratin in the identification of epithelial cells in lymph nodes.
215 INTER-EXAMINER REPRODUCIBILITY OF ANORECTAL MOTOR AND SENSORY FUNCTION TESTS
T.J. Nicholls, D. Solanki, T. Mimura, A.V. Emmanuel, M.A. Kamm.Physiology Unit, St Mark's Hospital, London, UK
Background: Anorectal physiological tests are used to influence management of benign anorectal disorders. However their inter-examiner reproducibility has not been well established. We assessed statistical reproducibility and reproducibility with respect to clinical significance.
Methods: 37 consecutive patients referred for routine anorectal physiological tests were studied by two investigators, unaware of the other's results, in random order, 30 minutes apart. Maximum anal canal resting (MRP), squeeze (SP) and involuntary contraction pressures (CP, pressure generated on coughing) were assessed using a water perfused manometry system; anal canal (AS) and rectal mucosa sensitivity (RS) to electrical stimulation using a bipolar ring electrode. (i) Inter-examiner reproducibility was assessed using the method by Bland and Altman (Lancet 1986, 1:307–310). The difference in measurements between 2 investigators was plotted against the average measurement of both investigators for each of the described tests, after a log transformation. (ii) Reproducibility with respect to clinical result (how often result was consistently within or outside the normal range) was also assessed.
Results: (i) For all the measured variables the largest differences between observers were found when the means were greater, which demonstrates that the data from the two investigators were in statistical agreement, and suited to log transformation. All measured parameters, apart from CP, were significantly reproducible. (ii) The percentage of inter-examiner results showing consistency in relation to a normal or abnormal outcome (within or without 2SD of normal mean) were: MRP 92%, SP 78%, CP 62%, AS 84%, RS 95%.
Conclusions: All tests, apart from CP were statistically reproducible. Therefore when these tests are performed using the same standardised technique one can have confidence in the numerical accuracy of the result. These tests are also usually consistent in producing a result which is abnormal, and therefore of particular clinical significance. CP provides only a rough guide to pelvic floor contraction, but is not a precise measurement. It may be best used as present or absent above a certain level.
216 HYPNOTHERAPY FOR IRRITABLE BOWEL SYNDROME: IMPROVEMENT IS LONG-LASTING AND REDUCES HEALTHCARE COSTS
W.M. Gonsalkorale, V. Miller, A. Afzal, P.J. Whorwell.Dept of Medicine, University Hospital South Manchester, M20 2LR, UK
Background: We have shown that hypnotherapy (HT) improves symptoms and quality of life (QOL) in patients with irritable bowel syndrome (IBS). This is now provided as a clinical service and this study presents long-term follow-up on a large group of patients treated.
Method: 239 IBS patients who had undergone HT between 1 and 5 years ago were contacted and asked to complete i) a validated IBS Questionnaire rating severity of symptoms and QOL (visual analogue scales), ii) the Hospital Anxiety and Depression (HAD) Scale, (both previously completed pre- and post-HT), iii) a Subjective Assessment Questionnaire (SAQ) assessing effects of hypnotherapy, medication use and consultation rates.
Results: 178 patients returned questionnaires (74% response rate). In the SAQ, 86% of patients had improved at the end of HT (62% of whom rated symptoms as very much better). 83% of these reported that, since finishing HT, symptoms had remained the same as at the end of HT or had continued to improve, while 17% had some deterioration. In addition, 59% of patients did not require any medication and 40% of those who did took it less often than previously. 75% consulted their GP and/or a hospital consultant less often about IBS symptoms and 49% less about other symptoms. All IBS measures in the IBS Questionnaire remained significantly better at follow-up than before HT (all p<0.001), with only slight deterioration in some compared with post-HT [pre-HT v post-HT v follow-up, median (IQR): pain severity: 54(37,75) v 25(10,50) v 33(18,50); pain frequency: 50(30,90) v 20(5,50) v 20(1,58); bloating: 62(50,80) v 25(7,50) v 39(23,50); bowel habit dissatisfaction: 74(58,97) v 35(27,52) v 38(33,66); life interference: 75(65,89) v 33(22,60) v 39(30,65); forming an overall score: 314(258,287) v 156(91,249) v 171(118,268)]. Extra-colonic symptoms, QOL and HAD scores all also remained improved (all p<0.001).
Conclusion: This study confirms the long-term benefit of HT. In addition, the substantial reduction of medication and consultation rates highlights the significant economic advantages of this form of treatment.
217 A PROSPECTIVE RANDOMISED CONTROLLED TRIAL OF CONSERVATIVE MANAGEMENT VERSUS OPERATION IN PROLAPSED THROMBOSED HAEMORRHOIDS
A.P. Malalasekera, G. Ratnayake, K.I. Deen.Professorial Unit of Surgery, Faculty of Medicine, Kelaniya, Sri Lanka
Introduction: Conservative management has been the mainstay of treatment of prolapsed thrombosed haemorrhoids (PTH). The aim of our study was to evaluate the role of operative management for PTH in a randomised trial.
Methods: Fifty consecutive patients (male - 43; median age - 43 years; range – 23 to 76 years) were allocated to receive either conservative management or operation by computer generated random tables. Those managed conservatively (bedrest, analgesics, osmotic packs) who failed to respond after 5 days were offered haemorrhoidectomy. End points assessed were: pain (visual analogue scale 0–10), outcome of treatment, duration of hospital stay, urinary retention and bleeding complications.
Results: Median (range) pain score in those with PTH receiving conservative management was 5 (0–10) compared with a median score (range) of 5 (0–10) following haemorrhoidectomy (P >0.05, N.S.). Conservative measures were successful in 13 (52%) of twenty-five patients compared with 24 (96%) of twenty-five patients who received operation (P < 0.05 – test of proportions) for prolapsed thrombosed haemorrhoids. Duration of hospital stay (median, range) in the conservative group was 8 days (2–10) compared with 5 days (2–6) in the operative group. Urinary retention was seen in 1 (4%) in the conservative group versus 3 (12%) in the operative group (P>0.05, N.S.) whilst bleeding complicated operation in one patient (P>0.05, N.S.).
Conclusion: Compared with conservative treatment, operative treatment of prolapsed thrombosed haemorrhoids resulted in symptom cure in a significantly greater proportion of patients. Furthermore, duration of hospital stay was less in those receiving operation. Even though there was a tendency towards a higher rate of urinary retention and bleeding after operation it was not statistically significant. We recommend haemorrhoidectomy as the treatment of choice for prolapsed thrombosed haemorrhoids.
218 ELECTIVE COLECTOMY FOR DIVERTICULAR DISEASE?
K. Somasekar, P.N. Haray, M.E. Foster (introduced by P.S. Davies).Royal Glamorgan Hospital, Llantrisant, Mid Glamorgan, Wales, UK
Introduction: Colonic diverticular disease is a common problem in the Western world. Studies about the natural history of diverticular disease and the incidence of complications after an initial attack have reported varying outcomes. This has led to a debate on the value of elective colectomy in preventing complications of diverticular disease.
Aim: To assess whether the complications of diverticular disease requiring emergency or urgent surgical intervention are related to previous episodes of diverticulitis and if elective colectomy might prevent such complications.
Methods and Materials: A retrospective analysis was performed of all the patients who were admitted with complicated diverticular disease in two adjacent district general hospitals between 1995–2000 and information was recorded on the past history of these patients with regard to previous investigations or treatment for diverticular disease.
Results: A total number of 108 patients (42 males and 66 females) were admitted with complicated diverticular disease. Ninety eight patients (91%) were emergency admissions and 10 patients (9%) were urgent admissions. Ninety eight patients (91%) underwent a Hartmann's procedure. Two patients had a subtotal colectomy and 4 patients had a sigmoid colectomy with primary anastamosis. Four patients were not operated on due to their poor general condition. Out of the 108 patients, only 28 patients (26%) were previously diagnosed to have diverticular disease, either by barium enema or endoscopy. Eight of the twenty eight patients had required previous admissions for acute exacerbation of their symptoms, 3 having been admitted twice. Only 3 patients (2.7%) had needed treatment for acute diverticulitis with intravenous fluids and antibiotics.
Conclusions: Our study has shown that elective colectomy after an attack of diverticulitis would not have a significant impact on the incidence of complications as most of them occur de novo in patients with no previous history of the disease. Further prospective studies are needed in those with known diverticular disease to identify any further risk factors for development of future complications. This would help to identify a group of patients who may benefit from elective colectomy.
219 GASTROINTESTINAL SYMPTOMS AFTER RADIOTHERAPY FOR PELVIC CANCER
H.J.N. Andreyev, Z. Amin, P. Blake, D. Dearnaley, D. Tait, P. Vlavianos.Imperial College Faculty of Medicine, Chelsea & Westminster & Royal Marsden Hospitals, London, UK
Introduction: About 13,000 patients undergo pelvic radiotherapy annually in the UK. The incidence of severe GI toxicity (fistulation, bowel obstruction, transfusion dependent bleeding or secondary cancer) is not known but probably occurs in 4–8% at 5 years. More common are symptoms such as incontinence or diarrhoea which may significantly impair quality of life in >30% of long term survivors.
Aim: To describe the symptoms and outcomes of patients following pelvic radiotherapy referred to a specialist gastroenterology/ GI oncology clinic during its first year.
Methods: Oncologists were offered direct flexible sigmoidoscopy for any patient with bright rectal bleeding without other symptoms, irrespective of proctoscopic findings. Other patients were reviewed in clinic. Data were recorded prospectively.
Results: Over 12 months, 60 patients were referred: 37 men, 23 women with a median age 64 years (range 38–80). Primary tumours sites included prostate (n=33), cervix (n=12), endometrium (n=7), bladder (n=3), large bowel (n=2), and anus, vagina and ovary (n=1 each). Radiotherapy was given a median 2 (range 0.5–21) years previously except in 3 patients referred to exclude inflammatory bowel disease before starting treatment. Major symptoms included rectal bleeding (n=27), frequency (n=22), faecal incontinence (n=19), diarrhoea (n=14), pain (n=8), steatorrhoea (n=5), subacute obstruction (n=4) and tenesmus (n=3). Eight patients described significantly abnormal bowel habit before starting radiotherapy. Of patients with bleeding alone (n=19), 1 had no radiation proctitis but was bleeding from mucosal prolapse, 3 had unsuspected advanced adenomas and 2 had squamous polyps. Sucralfate was always effective in reducing bleeding in those with radiation proctitis. All patients with tenesmus or incontinence improved or were cured with medical therapy including 2 patients with marked anal sphincter changes on endoanal ultrasound. Steatorrhoea was multifactorial, (2, bacterial overgrowth, 2 pancreatic insufficiency, 2 fatty acid malabsorption). Pain was associated with relapse in 50%. Two patients with obstruction required surgery.
Conclusions: Chronic GI symptoms after radiotherapy are often highly debilitating and complex to assess, but may respond dramatically to simple combination therapies. Patients with new onset rectal bleeding following radiotherapy should be offered at least a flexible sigmoidoscopy. Patients appear to benefit from being seen in a specialist setting.
220 TIMING OF OPERATION AFTER RADIOTHERAPY FOR RECTAL CANCER
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: Preoperative adjuvant radiotherapy for rectal cancer has two problems, radiosensitivity and timing of operation. We have examined the effect of radiation and its timing on the relationship between apoptotic cell index (AI) and proliferative activity index (PI).
Methods: Patients were given one of three alternative modalities, standard radiotherapy (SD) (40Gy, duration of 4–8weeks, n=23), short-course radiotherapy (SC) (25Gy, 1–2weeks, n=11), or chemoradio-therapy (CR) (45Gy, 6–9weeks , n=7). AI and PI were estimated in paired sections of biopsies and post-irradiated resected tumours. The reduction ratio was histologically estimated and radiosensitive was judged in cases in which over 2/3 of tumour tissue was destroyed
Results: Radiosensitive ratio and median reduction ratio were 43.5% and 45% in SD, 27.3% and 25% in SC, 28.6%and 45% in CRT, respectively. In SD, the AI was significantly higher (5.9 v.s 2.7; p= 0.001) and the PI was significantly lower (33.9 v.s 50.0; p=0.028) than in the pre-therapy biopsies. In SD, the PI in the radiosensitive subgroup was lower than in the radioresistant one (25.9 v.s 46; p=0.005)). However, the AI of radiosensitive subgroup was lower than that of resistant one (2.4 v.s 4.2; p=0.005). Plotting each AI according to time course from finishing radiotherapy to operation in SD showed that the slope of in the radiosensitive subgroup was steeper than in the radioresistant one and extrapolation back to the end of radiotherapy (day 0), suggests that in the radiosensitive subgroup would have a high AI. The difference between two slopes means that in radiosensitive subgroups, the apoptotic response rapidly came and went. Plotting the AI against reduction ratio revealed that the AI was proportional to the size of the residual tumour volume (low in the radiosensitive).
Conclusions: Apoptosis may be a time-limited and volume-dependent phenomenon; radiosensitive tumours should be surgically resected earlier than the more resistant ones.
221 RANDOMISED CONTROLLED TRIAL OF BIOFEEDBACK FOR FAECAL INCONTINENCE
C. Norton, S. Chelvanayagam, M.A. Kamm.St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK
Background: Behavioural treatment (biofeedback) has been reported to improve symptoms in a majority of patients with faecal incotinence, but there are no trials comparing biofeedback with placebo or standard medical care.
Methods: 171 consecutive patients with faecal incontinence to solid or liquid stool were assessed by anal ultrasound and then stratified to structurally intact or disrupted anal sphincter muscles. Within each of these two groups they were then randomised to one of four groups: (1) standard medical/nursing care (advice) (2) advice plus verbal instruction on sphincter exercises (3) hospital based computer-assisted sphincter pressure biofeedback (4) hospital biofeedback plus use of a home EMG biofeedback device. Outcome measures immediately and at one year included diary, symptom questionnaire, continence score, patient's rating of change, quality of life (SF36 and disease specific), psychological status (HAD), and anal manometry.
Results: Improvement or cure occurred in groups 1 to 4 respectively: 80%, 83%, 81%, and 76% (p=NS). Overall, 75% of patients had symptomatic improvement and 5% were “cured”. Major benefit was more likely if patients had structurally intact sphincters. Benefit was maintained for all groups at one year. Episodes of incontinence decreased from median 2 to 0 per week (p<0.001). Continence score (worst = 20) decreased from median 11 to 8 (p<0.001). Disease specific quality of life, SF36 (vitality, social functioning and mental health), and HAD (anxiety and depression) all significantly improved. Patients demonstrated improved resting, squeeze and sustained squeeze pressures (all p<0.002). None of these improvements differed between groups.
Conclusions: Conservative therapy for faecal incontinence improves continence, quality of life, psychological well being, and sphincter function. Benefit is maintained in the medium term. The patient-therapist interaction and improved coping strategies appear to be most important, rather than physiological feedback of sphincter function (biofeedback).
222 FAECAL CALPROTECTIN: NORMAL LEVELS IN A LATE MIDDLE-AGED POPULATION, EFFECTS OF LIFESTYLE FACTORS AND RELATION TO BOWEL SYMPTOMS
A. Poullis1,2, R. Foster2, A. Shetty1, T.C. Northfield2, M.K. Fagerhol3, M.A. Mendall1.1Mayday University Hospital;2St George's Hospital Medical School;3University of Oslo, Norway
Background: Faecal calprotectin is more sensitive but less specific than faecal occult blood (FOB) in the detection of colonic neoplasms (Tibble et al, Gut 2001). Little is known about levels in a late middle aged population, which would be the target for screening, and factors that determine levels. Furthermore it is unknown whether elevated levels are associated with symptoms, diarrhoea in particular.
Aims: To assess levels of faecal calprotectin and the factors that could effect them in a healthy late middle aged population and to assess the association with symptoms.
Methods: 230 asymptomatic subjects (155 male, 75 female) aged between 50 and 70 were recruited randomly from GP lists in South London. Subjects with IBD or a history of colorectal cancer (CRC) were excluded. A previously validated lifestyle questionnaire was completed and a stool sample analysed for calprotectin by ELISA.
Results: Faecal calprotectin was bi-modally distributed, with 46/230 (20%) of subjects having levels above the reference range (10mg/l). There was no association between NSAID use, units of alcohol consumed in the previous week, being a present smoker, daily bowel frequency, and presence of abdominal pain or constipation in the previous week and faecal calprotectin. Males had higher calprotectin levels than females (median 1.9 IQR 7.6 v 0.5, 2.8 p<0.0001). 65% of subjects in the 3rd calprotectin tertile (C.T.) were past smokers v 45% of subjects in 1st C.T. (p=0.06). Mean cigarette pack years of smoking increased through each C.T. 9.8, 10.5, 17.9 (p=0.009). 20% of subjects in the 3rd C.T. had suffered an episode of diarrhoea in the previous week v 12% in the 1st C.T. (p=0.05). Mean age increased in each C.T. 58.9,60.5,60.8 (p=0.03).
Conclusion: Smoking history, diarrhoea in the previous week, increasing age and male sex are all associated with an increasing faecal calprotectin. Adjustment of values for the above variables may increase faecal calprotectins specificity as a screening marker for CRC.
223 IS CONSTIPATION A CONSEQUENCE OF GROWING OLDER?
C. Eastwood, G.J. Davies, P.W. Dettmar1.Nutrition Research Centre, South Bank University, London, UK;1Reckitt Benckiser Healthcare (UK) Limited, Hull, UK
Background: The number of GP visits for constipation increases markedly among people over 60. Nevertheless, there is no good evidence that ageing per se affects colonic function. The association between age and constipation may be confounded by factors such as institutionalisation, inactivity and chronic disease.
Aim: To assess the prevalence of functional constipation according to the Rome II diagnostic criteria and institutionalisation, physical activity and chronic disease.
Methods: Ethical approval was obtained from South Bank University Ethics Committee. 50 FL subjects (mean age 74 years, range (65–97), 42% male) and 42 INS subjects (mean age 84 years, range (69–101) 36% male) were recruited. Bowel habit was recorded using a 7-day bowel habit diary. Subjects were classified as constipated according to Rome II diagnostic criteria, if they experienced at least two of the following: less than 3 defecations per week, straining on more than 25% of occasions, feelings of incomplete evacuation on more than 25% of occasions. Statistical analyses were performed using the t-test and Chi-square, as appropriate.
Results: Since the INS group was significantly older than the FL group, the mean ages of constipated and non-constipated subjects were assessed in each group separately. There were no significant differences in age between constipated and non-constipated subjects. Constipation was associated with institutionalisation (κ2=9.9; p=0.003) and inactivity (κ2=12.2; p=0.001). Although 65% of constipated subjects suffered from more than one chronic disease, this association was not statistically significant.
Conclusions: This study suggests that the prevalence of functional constipation is associated to factors related to ageing such as institutionalisation and inactivity. However, no association was found with chronic diseases.
224 K-RAS MUTATIONS IN COLORECTAL POLYPS: SITE, HISTOLOGY AND SIZE DO MATTER
G.L. Williams1,2, G.J. Jenkins2, J.M. Parry2, J. Beynon1.1Dept of Colorectal Surgery, Singleton Hospital, Swansea, UK;2School of Biological Sciences, Swansea University, UK
Introduction: Mutation of the oncogene K-ras is thought to be important in the early progression of colorectal carcinogenesis. K-ras is involved in the cell signalling pathway and its mutation causes uncontrolled cell proliferation The aim of our study was to assess the relationship between K-ras mutations and various characteristics of colorectal polyps such as: site, size and histology.
Methods: Polyps were collected during colonoscopy from 55 successive patients and control tissue obtained from 20 other patients. DNA was extracted from the fresh tissue and mutations were detected following PCR and restriction enzyme (mva1) digestion. Ethical approval was obtained.
Results: Mutations of K-ras were found in 21% of the 55 polyps; none of the controls had mutations. Of the 15 rectal polyps 33% had a mutation; whereas only 18% of the 40 colonic polyps had a mutated K-ras. 36 polyps were <1cm (mutation rate 8%) and 19 polyps were >1cm. These larger polyps had a higher K-ras mutation rate of 47%. Histological type was also analysed, revealing that 30% of tubulovillous/villous polyps had a mutation, compared to much lower levels of mutations in tubular (9%) and metaplastic polyps (0). No difference in mutation rate was found in varying grades of dysplasia in our study.
Discussion: This small study reveals that K-ras mutations in our population tended to be associated with polyps having a rectal location, a larger size and villous histology. Further studies are needed to understand the role of this important oncogene in adenoma growth and progression to carcinoma.
225 DO CYTOKINE LEVELS PREDICT PROGNOSIS IN COLORECTAL CANCER?
A.G. Prabhudesai, A.G. Heriot, J.B. Marriott, A.G. Dalgleish, D. Kumar.Departments of Colorectal Surgery and Oncology, St George's Hospital, London, UK
Suppression of the immune system and cytokine production, as an essential function of the immune response, in patients with colorectal cancer has been extensively investigated. The aim of this study was to determine the predictive prognostic value of cytokine levels before & after treatment in patients with colorectal cancer.
Methods: Heparinized venous blood samples were taken from fifty-three patients (34M &19F) with primary colorectal cancer before and at least 10 weeks after operation. Patients who had preoperative radiotherapy had blood samples taken before radiation therapy. Interferon (IFN) γ, Interleukin (IL) 10 and Tumour necrosis factor (TNF) α levels were measured by lipopolysaccharide stimulated blood cultures. The patients were followed up in a Colorectal Cancer Clinic for evidence of local recurrence, distant metastases and survival.
Results: Patients with high preoperative levels of IFN γ developed distant metastases later than those with lower levels. (Correlation coefft=0.812 at P=0.05) Similarly, those with high postoperative IFN γ levels developed local recurrence later than those with lower levels. (Correlation coefft =1at P=0.01;) IL 10 & TNF α levels did not show a similar correlation. Higher levels of postoperative IL 10 levels were associated with development of metastatic disease. (Correlation coefft=-0.853 at P=0.002) Higher TNF α levels before preoperative radiotherapy were associated with a longer survival in patients with rectal cancer. (Correlation coefft=0.829 at P=0.04) Similar TNF α levels without preoperative radiotherapy did not appear to confer the same survival advantage.
Conclusions: Higher levels of pro-inflammatory cytokines (TNF α, IFN γ) were associated with a better outcome in terms of time to local recurrence, distant metastases and survival. Higher levels of immunosuppressive cytokine (IL 10) were related to the development of distant disease. Those with lower levels of pro-inflammatory cytokines before treatment, and those with higher postoperative levels of immunosuppressive cytokines need close surveillance for the development of locoregional or systemic relapse.
226 SUCCESS OF A SIMPLE “TICK BOX” GP REFERRAL FORM FOR COLORECTAL CARCINOMA AND ITS IMPACT ON ACHIEVING THE “2 WEEK WAIT” TARGET
T. Thresher, J.D. Linehan, D.C. Britton, M. Davis, J.J.T. Tate, M.E.R. Williamson.Royal United Hospital, Combe Park, Bath BA1 3NG, UK
Introduction: In June 2000 the UK government introduced the target that a hospital specialist should see all patients with suspected GI cancer within 2 weeks of GP referral. With unlimited resources, all patients with any symptoms could be seen and immediately investigated, but in the UK methods to stratify patients in terms of risk of serious pathology are needed to ensure urgent investigation of patients at the highest risk.
Methods: We introduced a simple 10-question tick-box GP form for referral of all patients with rectal bleeding and change of bowel habit, which could be e-mailed or faxed directly to the endoscopy department. The responses allowed stratification of patients without prior assessment in outpatients into 3 groups. Patients stratified as “urgent” were sent a colonoscopy appointment for <2 weeks, “soon” for <12 weeks and routine for <36 weeks. Performance of the form has been audited over the 12 months following introduction. This included monitoring for time to colonoscopy from referral and accuracy of the form in predicting serious pathology (colorectal carcinoma, IBD).
Results: In total 691 referrals were made, of which 156 were stratified “urgent”, 447 “soon” and 88 “routine”. 73% of urgent patients achieved a colonoscopy in <2 weeks and 94% within 3 weeks including at peak holiday times e.g. Christmas etc. Those not done in <3 weeks were sent appointments but failed to attend. 97% of soon patients were colonoscoped in <12 weeks and 100% of “routines” in <36 weeks. See table⇑.
Conclusion: This referral form has proved successful in identifying patients at high risk of significant pathology and has allowed appropriate targeting of resources for rapid diagnosis of pathology without prior outpatient assessment. Rates of detection of serious pathology in “soon” and “routine” referrals were not significantly higher than those that would be anticipated in a comparable unselected population.