192. THE ANTEGRADE CONTINENCE ENEMA (ACE) PROCEDURE IMPROVES QUALITY OF LIFE IN CHRONIC CONSTIPATION AND FAECAL LEAKAGE

Introduction: The Malone reversed appendicocaecostomy was first introduced in 1993 for the treatment of faecal leakage in children and is well established in paediatric surgery. We describe our experience of 10 adults who have undergone an appendicocaecostomy to facilitate ACE for chronic constipation and faecal leakage.

Methods: 10 adults underwent appendicocaecostomy. They were retrospectively reviewed from case notes and stoma nurse records. Quality of life (QOL) was assessed in postoperative patients and compared with the cohort of patients awaiting the surgery using the validated SF-36 QOL survey.

Results: 10 patients (8 female) mean age 29 have undergone the procedure. 7 laparoscopically. 6 had a history of lifelong chronic constipation, 3 faecal leakage and 1 a mixed picture. Post operatively all recovered well from the initial procedure. All feel their presenting symptoms have improved but minor technical difficulties with the enema procedure are commonplace and good stoma therapist support is necessary. 2 had minor revision surgery of the stoma, 4 stricturoplastys and 1 became constipated again because of enema difficulties. QOL comparisons in the two groups has shown a significant improvement in the mean mental component score (MCS) on the SF-36 from 36.28 to 48.0 (p=0.038) and an improvement albeit not statistically significant in the physical component scores (PCS) from 36.28 to 43.8 (p=0.099).

Discussion: Adult ACE procedure is technically simple and effective in the treatment of constipation and faecal leakage. Significant improvement in the mean mental component score measured by the SF-36 is achieved.

193. THE ROLE OF AN INTRA-ANAL TAMPON FOR FAECAL INCONTINENCE; PRELIMINARY RESULTS OF A PROSPECTIVE STUDY

The surgical treatment of faecal incontinence is not always successful. Some patients continue to complain of incontinence after operation and others wish to explore non-operative means to improve their quality of life. We have assessed the efficacy and acceptability of an intra-anal tampon (IAT) in 50 patients studied prospectively with anal incontinence before and one month after the IAT using the Cleveland Clinic Incontinence Score (CIS) and the Minneapolis Quality of Life Score (MQOL). One patient could not tolerate the tampon and all except 6 patients reported some discomfort whilst 16 complained of perineal pain during its use. Nevertheless, CIS was significantly improved from 13.7 (7–18) to 11.9 (4–17) (p=0.007). Furthermore, MQOL also significantly improved for lifestyle from 18 (11–38) to 21.4 (15–39) (p=0.02) and for behaviour 13.5 (10–31) to 17.5 (11–32) (p=0.001) and for embarrassment 5.8 (3–11) to 7.1 (5–11) (p=0.02) but not for depression. Twenty six (52%) stated that they wished to continue to use the IAT because it improved their quality of life. Thirty patients reported that they would recommend the device to other people. This study has indicated that the IAT is safe but causes some discomfort but for those who continue to use the device quality of life is improved.

194. CAUSES AND TREATMENT OF MALE FAECAL INCONTINENCE

Introduction: Faecal incontinence in women has been extensively studied however there are few data on causes and outcome in men with this condition.

Aims: To analyse the causes, treatment and effectiveness of treatment for faecal incontinence in men.

Methods: We retrospectively reviewed the casenotes of men investigated for faecal incontinence between 1995 and 1999. The aetiology of incontinence and the outcome of treatment was examined.

Results: Records of 42 men (mean age 57 years, range 14–79) were reviewed. 19 (45%) had a history of anal surgery (haemorrhoidectomy 9, fistula surgery 5, abscess drainage 2, stretch 1, sphincterotomy 1). Eight (19%) had neurological problems, 3 related to spinal surgery and 1 to trauma. Two patients had a rectal prolapse, 1 a megarectum and the cause was not clearly defined in the remaining 12 (29%). Follow-up data was available in 35 cases. Thirty (83%) were treated conservatively, of whom 27 (90%) achieved a satisfactory improvement or complete resolution. Only 5 patients had surgical intervention (prolapse repair 2, graciloplasty 1, sphincter repair 1, colostomy 1).

Conclusions: Anal sphincter damage after anorectal surgery was the commonest cause of faecal incontinence in this group. Overt neurological disease was common and the aetiology was unclear in a significant number. Simple conservative measures lead to a satisfactory outcome in the majority of patients.

195. CLOSED LATERAL SUBCUTANEOUS SPHINCTEROTOMY UNDER DIRECT ENDOSONOGRAPHIC CONTROL

Closed lateral subcutaneous sphincterotomy (CLSS) is the procedure of choice for chronic anal fissure because healing rates are high but there is a small risk of transient or permanent impaired continence. This study was undertaken to determine if CLSS under direct endosonographic control (CLSSEC) is more effective and safer than standard CLSS. Thirty patients had CLSSEC and 20 had CLSS. The groups were comparable for age, sex and duration of follow up, all patients underwent clinical and anorectal phsyiological evaluation before and three months after the operation. Endoanal ultrasonographic was used before and after operation to assess the completeness of sphincterotomy. Fissures healed in all CLSSEC patients, whereas 2 persisted or recurred after CLSS. Impaired continence to flatus or soiling at one month was observed in 7 (23%) after CLSSEC compared with 4 (20%) after CLSS. Only 1, a CLSSEC patient, had persistent impaired continence at three months. Ultrasound revealed a complete internal sphincter defect in all CLSSEC patients but in only 4 of 10 in the CLSS group. The fall in resting pressure was greater after CLSSEC; 98.4 ± 31.2 to 63.1 ± 19.4; p=0.02 than after CLSS; 94.9 ± 27.3 to 76.5 ± 20.1; NS. These data indicate that CLSSEC is a more precise method of sphincterotomy but does not eliminate the risk of transient or even permanent impaired continence.

196. INCIDENCE AND SIGNIFICANCE OF A PREVIOUS HYSTERECTOMY IN WOMEN ATTENDING FOR ENDOSCOPIC INVESTIGATION OF LOWER GI SYMPTOMS

Background: The incidence of hysterectomy (HY) in women with lower GI symptoms attending for flexible sigmoidoscopy (FS) and its effect on the success rate of the procedure has not been formaly studied.

Aims: To prospectively estimate HY incidence in women attending an endoscopy clinic with lower GI symptoms. Secondly determine if HY affected FS success rate or caused detectable differences in pelvic loop size/configuration as a result of pelvic adhesions.

Methods/Results: Over a 12 month period a single experienced endoscopist carried out 2 “fast track” surgical endoscopy lists per week. Non-sedated FS was carried out in 200 women using either a full-length adult or 130 cm paediatric colonoscope. The FS failure rate (defined as inability to reach the sigmoid/descending colon junction or beyond) was significantly higher (p=0.0112) in HY patients (16/54 or 30%) compared with 19/146 (13%) in the women with no HY history. Using magnetic endoscope imaging (MEI) combined with a painometer (Gut 2000;46(suppl II A30) we showed that HY patients tended to form smaller/ tighter (and hence more painful) pelvic loops than other women. Furthermore when using an adult colonoscope (but not a floppier paediatric instrument) to perform FS, the median insertion depth before pain was first felt was significantly less (p=0.0002) in the HY patients.

Conclusion: Over 25% of female patients attending for lower GI investigations will have had a previous hysterectomy. A thinner/less stiff paediatric colonoscope is recommended for such patients.

197. A PROSPECTIVE STUDY TO ASSESS THE IMPLEMENTATION OF A FAST-TRACK SYSTEM TO MEET THE TWO-WEEK TARGET FOR COLORECTAL CANCER

Aims: This prospective study assesses the intoduction of a fast-track referral system for patients with suspected colorectal cancer.

Methods: The referral system was initiated in Yeovil District Hospital and Taunton and Somerset Hospital using six screening criteria to select high-risk patients. Data on all high-risk patients from 1 November 1999 to 30 April 2000 was recorded prospectively. Patients with proven colorectal cancer diagnosed between 1 November 1998 and 30 April 1999 have been identified for comparison.

Results: 433 fast-track referrals were received in the six month period, with 303 patients (70%) seen within two weeks.There were 158 new cases of colorectal cancer in total (111 elective, 47 emergency). 59 patients were diagnosed from fast-track referrals (53% of total elective cases). Median time to diagnosis in the fast-track group was 11 days versus 32.5 days for non-fast-track elective cases (p<0.001). Median time to diagnosis for all elective cases was 17 days versus 38.5 days for patients presenting one year earlier (p<0.001). 75% of fast-track patients were diagnosed within two weeks, compared with 17% of non-fast-track elective patients (p<0.001). 48% of all elective patients were seen within two weeks versus 17% of patients presenting one year earlier (p<0.001). The proportion of emergency admissions was reduced from 40% to 30% (p=0.07) following the introduction of this system.

Conclusions: A fast-track system for suspected colorectal cancer has led to a significant reduction in the time to diagnosis, with the majority of cases diagnosed within two weeks.

198. IMPACT OF THE “2 WEEK RULE” ON THE TREATMENT OF COLORECTAL CANCER

The government has pledged that all patients with suspected colorectal cancer will be seen within 2 weeks and they have published guidelines to identify high risk patients. This study analysed patients with colorectal cancer admitted to a single surgeon with no referral guidelines. The number who would have met the guidelines and the potential effect on overall time to treatment was determined by assuming the time to first out-patient appointment for this group would have been a maximum of 14 days and adjusting time to diagnosis and treatment accordingly. The case notes of 78 patients (32 (40%) female, mean age 68 years (range 24–96)) were studied. 81% of 32 patients with rectal cancer and 67% of 46 with colon cancer met the guidelines. Adherence to the guidelines in patients with rectal cancer would have had a small but significant effect on the time to first appointment (median 8 days, interquartile range 3–35 days, reduced to 8 (3–14) days. Wilcoxon matched pairs p=0.016). Time to diagnosis would also be reduced (26 (6–61) vs 17 (6–40), p=0.016) but there would have been no effect on time to surgery (117 (86–149) vs 96 (62–145), p=0.06) because of prolonged waiting times for staging and pre-operative radiotherapy. Time to first appointment with colon cancer would have fallen (28 (9–49) days vs 14 (9–14), p<0.0001). Time to diagnosis (62 (22–104) vs 21 (14–67), p<0.0001) and treatment (120 (56–143) vs 56 (40–117), p<0.0001) would also have been significantly reduced. Implementation of government guidelines and the 2 week rule would have had significant benefits in terms of treatment times for patients with colonic but not rectal cancer. Their introduction needs to combined with increased resources for staging and radiotherapy due to achieve significant improvements for patients with rectal cancer.

199. AN AUDIT OF FAECAL OCCULT BLOOD TESTS IN A DISTRICT GENERAL HOSPITAL

Introduction: Faecal occult blood tests (FOBs) have been validated in colorectal cancer screening. Their value in other indications is less clear. Despite this use of FOBs remains commonplace.

Aims: (1) To audit FOB use with reference to their source, indications and results. (2) To determine if FOBs altered in-patient management.

Methods: Computerised records of FOB requests received by the biochemistry department in 1997 were retrospectively reviewed. For in-patient requests hospital notes were reviewed to determine outcome and what influence the FOBs had on management.

Results: 1497 FOBs from 630 patients (516 from primary care). 58.5% of hospital patients (HP) v 28.8% of primary care patients (PC) were positive (p<0.001). Median age 63 (1 month to 100 years). Complete collections of 3 faecal samples were greater in PC than in HP (61.8% v 36.0%; p<0.001). Indications from PC were anaemia 32.8%; frank GI bleeding 9.9%; altered bowel habit 20.7%; abdominal pain 13.8%; others 10.3%. An indication was not supplied in 12.4%. 15 of 121 GPs were responsible for 37% of primary care requests. Indications for HP were anaemia 43.9%; frank GI bleeding 18.4%; altered bowel habit 12.0%; abdominal pain 7.0%; others 14.9%. Elderly care wards 42 (36.8%); general surgery 25 (21.9%); nephrology 16 (14%); others 31 (27.2%). Decisions to send FOBs were made by nurses in 18 cases. Case notes of 86 in-patients were reviewed (remaining 28 unavailable). Further management was determined on the basis of FOBs in 14 of 53 positive and 20 of 33 negative cases (GI imaging, specialist referral, repeat FOBs, no investigation). 23 positive and 4 negative FOBs did not appear to have been reviewed by clinicians. GI diagnoses were made in 23 positive cases (3 colorectal cancers). GI diagnoses were also made in 12 cases in spite of negative FOBs (1 small bowel lymphoma). In these 35 cases pathology was found throughout the GIT.

Conclusions: FOBs are used for a wide range of non-validated indications. A few GPs & hospital sub-specialities are responsible for a disproportionate number of requests. In the majority of hospital patients FOBs add little to overall management.

200. IMPACT OF THE NURSE LED RECTAL BLEEDING CLINIC

Background/Aims: Rectal bleeding is a common symptom referral often necessitating multiple hospital visits for initial assessment, investigation and subsequent management. Recently there has been a heightened awareness of colorectal cancer leading to an increased service demand. To meet this demand a nurse led open access rectal bleeding clinic was set up to provide a fast-track service to examine, treat and discharge patients with benign anorectal conditions and screen for neoplastic disease in a single session.

Methods: A rectal bleeding clinic was established in August 1999. Patients over the age of 45 with symptoms of bright red rectal bleeding only were referred directly by their GP to the Endoscopy unit. Referral letters were screened by a Consultant surgeon (ACW) and appointments arranged within a 4 week period. A full history and physical examination was performed with flexible sigmoidoscopy and video proctoscopy in all patients. Those with benign ano-rectal disease were treated and discharged on the same day. Patients with normal findings were referred for barium enema and in those with adenomatous polyps colonoscopy was performed. Patients were followed up at 1 and 5 year intervals.

Results: 220 patients were referred (118 male, 102 female, mean age 55.9yr (sd=14.8). Indications: rectal bleeding (90%), 9% of referrals included bleeding/anal pain and bleeding/change in bowel habit (1%). Findings: benign ano-rectal disease (45%) (injection of haemorrhoids in 10%), diverticular disease/IBD (17%), polyps (adenomas>1cm) (10%) (median age 54yr (45–68); mean no. of polyps 1), cancer (2%) (median age 75.5yr (70–88)), and normal examination (26%). Of the cancers/polyps (4%) were within reach of a rigid sigmoidoscope (at 20cm). The remaining (96%) cancers/polyps were found in the distal/proximal sigmoid and descending colon. 45% of these patients also had co-existent haemorrhoids. 20 patients have been followed up at their one-year interval; only two have been re-referred for treatment of their haemorrhoids and discharged. Routine outpatient waiting times have been reduced from 16 to 8 weeks.

Conclusion: All patients with symptoms of rectal bleeding require at least a flexible sigmoidoscopy to exclude neoplastic disease. A nurse led clinic provides an effective ‘one-session’ service reducing outpatient clinic waiting times.

201. THE CLEAR CAMPAIGN: PUBLIC ACCESS PR BLEEDING CLINICS-AN INITIAL REPORT

Background: Colorectal cancer (CRC) is the second commonest cause of UK cancer deaths. Our District General Hospital (West Yorkshire, UK urban/rural mix, population served 195,00–95,000 male) has developed a novel CRC campaign after being approached by a local charity group (Skipton Rotary Club). The CLEAR (Co L orectalEducation AndResearch) campaign aims are to increase public awareness of symptoms of CRC and support a new rapid access per rectum bleeding clinic. We describe the CLEAR clinic development and initial analysis comparing it with open-access flexible sigmoidoscopy clinics (OAFS).

Method: A pilot study of established OAFS was done from Dec ‘98 to Mar ‘99 inclusive. 158 patients (n=158) were scoped. 18 tumours and polyps (neoplasia) were found, as were 3 cases of inflammatory bowel disease (IBD). The most sensitive symptom was per rectum bleeding which identified 14 of the neoplasia and 2 of the IBD. This symptom is easily understandable to the public, and was made the criterion for access to the CLEAR clinic. Access is made by a telephone call directly from a member of the public to a CLEAR number, and the patient is seen at the next clinic (either fortnightly or monthly depending on demand). Initial rollout was to GPs who informed their patients of the clinic and how to access it if symptomatic, followed by a letterbox drop to households within the relevant postcode areas, also allowing patients to bypass GPs altogether (patient initiated). Clinics are between 5pm and 7pm for patient convenience.

Results: From Oct ‘99 to Oct ‘00 CLEAR (n=179) and OAFS (n=648) clinics have been directly compared. “PR bleeders” seen in OAFS are 45% cf. 56% in the pilot study - not significant (NS) - implying that this group has not simply been diverted to CLEAR clinics. There are significant differences in numbers of males presenting via OAFS and CLEAR (43% vs. 54% p=0.035). This points towards an under representation of males at OAFS (p=0.029 vs. population) which disappears at CLEAR (p=NS vs. population). Average ages were similar (56.4 at OAFS, 53.3 at CLEAR). At CLEAR clinics, 25 neoplasia and 5 IBD cases were identified cf. 91 neoplasia and 21 IBD at OAFS (p=NS).

Conclusions: Our population accepts public access clinics for per rectum bleeding. The pickup rate of significant pathology at these clinics is directly comparable to an established service. That more men attend these clinics may reflect both the change in clinic timing and the simplified access. There is no evidence of inappropriate testing with patient initiated direct access and our approach appears on initial analysis to increase service uptake by men.

202. TOPICAL L-ARGININE LOWERS RESTING ANAL PRESSURE

Introduction: Chronic anal fissure is associated with raised resting anal pressure (RAP). The discovery of nitric oxide as a neurotransmitter mediating relaxation of the internal anal sphincter, led to investigation of exogenous nitric oxide donors, such as glyceryl tri-nitrate (GTN) as possible treatments for anal fissure. Endogenous nitric oxide (NO) is produced from cellular metabolism of L-arginine by NO synthase. This study investigated whether topical L-arginine may lead to increased NO production and reduced pressures in healthy volunteers.

Method: Local ethics committee approval was obtained. Anal manometry was performed using a solid state catheter for 2 hours following application of 400 mg of L-arginine ointment to the anal verge in 15 volunteers. After a washout period of 2–4 weeks, 11 of the 15 volunteers repeated the study using a placebo gel (Aquagel) for a period of one hour.

Results: The pressure drop from the initial RAP is shown in the table below. Topical L-arginine caused a greater maximum fall in mean RAP than placebo (p=0.002, Mann-Whitney U, table 1).

Results are expressed as mean ± S.E.M. The ‘P’ value for the fall in RAP at each time point was calculated using Wilcoxon Rank Sign test.

Conclusion: Arginine effectively lowers RAP; its onset of action is rapid and duration at least 2 hours. Arginine shows promise as a possible alternative treatment for chronic anal fissure.

203. ILEAL POLYPS IN FAMILIAL ADENOMATOUS POLYPOSIS

Background: Restorative proctocolectomy with ileal pouch-anal anstomosis has become more common as a prophylactic procedure in familial adenomatous polyposis (FAP) because of the advantage of removal of all cancer-prone mucosa. The recent finding (Gastroenterology2000;118(suppl 2):A427), however, of adenomatous polyps of ileal origin arising in up to 66% of FAP pouches has prompted a closer inspection of FAP ileal mucosa which is not incorporated into a pouch

Aim: To demonstrate ileal adenoma at the time of colectomy for FAP.

Subjects and Methods: 12 patients with FAP were examined intra-operatively by passing a video-colonoscope into the ileum immediately after colectomy and before the anastomosis was made. The surgeon then manually fed the tip of the endoscope 60cm poximally. The site, number and size of ileal polyps were recorded. Four biopsies were taken from normal looking ileum and four from polyp or other suspicious mucosa, thereby following the same protocol for pouchoscopy. In addition, the resected ileal cuff adjacent to the caecum was examined histologically for adenoma.

Results: The median age at colectomy was 25.5 yrs (14 to 56) and number of macroscopically visible colonic polyps in the histological specimen 648 (143–1180). Six of the12 patients had visible ileal polyps up to 1cm in size but in all cases the lesions consisted of lymphoid hyperplasia, not adenoma. One of the biopsies from normal looking mucosa in one patient, and one of the resected ileal cuff specimens in another contained single-crypt and oligocryptal adenomas repectively.

Conclusion: The terminal ileum in these confirmed cases of FAP does not contain adenomatous polyps and has detectable microscopic adenoma only. This is in contrast to FAP pouch ileal mucosa in which visible and histologically confirmed adenomatous polyps are seen in two thirds of cases. Environmental changes (faecal stasis) associated with pouch formation may lead to growth of ileal adenomas. Incidence and nature of pouch adenomas in patients with familial adenomatous polyposis.

204. OUTCOME OF ANAL FISTULA SURGERY IN CROHN'S DISEASE

We have prospectively studied the results of operations for symptomatic anorectal fistulas (AF) in Crohn's disease (CD). Thirty patients with 37 AF and CD were studied clinically and using a continence score and anorectal physiological studies before and three months after operation; 18 women, mean age 37.8 (range 25–53 years). Three of 37 AF were superficial, 13 of 37 were inter-sphincteric, 20 of 37 were trans-sphincteric and 1 of 37 super-sphincteric. Thirteen AF were laid open and 24 were treated by a loose seton. Follow up was 2.1 years (range 0.8–2.6). In patients managed by lay-open, continence status deteriorated significantly; Cleveland Incontinence Score (CIS) deteriorated from 5.3 to 10.4 (p=0.0004); resting and squeeze anal pressures fell from 58.2 to 36.3 and from 78.3 to 59.6 respectively (p=0.006 and p=0.01). The volume of first leakage also fell from 529.6 ml to 312.7 ml. After loose seton, the CIS deteriorated only slightly from 4.2 to 7.1 (p=0.03); resting and squeeze pressures also fell from 50.2 to 43.2 and from 76.8 to 68.0 respectively (p=0.02 and p=0.02). The volume of first leakage fell from 512.1 ml to 398.2 ml. During the study period 22 of 30 AF healed in a mean time of 4.7 months (3.2 to 7.1). Laying open and AF in CD compromises continence more than the use of a loose seton. Furthermore, surgical treatment achieves healing in only three quarters of all patients.

205. SERUM B12 FALLS AFTER POUCH SURGERY BUT BACTERIAL OVERGROWTH IS NOT THE CAUSE

The long-term effect of totally stapled restorative proctocolectomy (TSRP) on vitamin B12 levels is unknown. We routinely measure vitamin B12 levels in our 164 patients, at follow-up after TSRP. Since bacterial overgrowth is suspected as a cause of B12 deficiency in these patients, hydrogen breath tests were performed on those with low serum B12. Three patients were B12 deficient prior to pouch formation. At follow-up thirty nine (23.8%) had low B12 (<188pg/ml), at a median of 2.4 years (0–7) of pouch function. In addition forty seven (73.4%) patients with multiple B12 measurements showed steadily decreasing levels. 34/35 (97.1%) patients with B12 deficiency who subsequently had a hydrogen breath test were negative for bacterial overgrowth (table 1).

These data show that almost one in four patients after TSRP will have low serum B12 within 7 years. We recommend lifelong follow-up of vitamin B12 levels. In this study, bacterial overgrowth does not appear to be the cause of this B12 deficiency.

206. PATIENT VERSUS PHYSICIAN DELAY IN COLORECTAL CANCER; CAN WE DO BETTER?

Background: Altered bowel habit and rectal bleeding are considered ominous symptoms. Negligence may cause considerable delay in diagnosis of colorectal cancers. We have prospectively analysed presenting symptoms, patient's delay, and physician's delay in colorectal cancer patients who were admitted to our unit.

Method: Questionnaire survey of time interval between onset of symptoms and first visit to physician and time interval from first visit to diagnosis of colorectal cancer.

Results: 63 patients (24 male; median age 60 years, range 23 to 78 years) were evaluated, 34 (53.9%) had rectal cancer, 12 (19%) had right colonic cancer, 11 (17.4%) had left colonic cancer and 06 (9.5%) transverse colonic cancer. Presenting symptoms in rectal cancer were (n=34): bleeding (n=27; 79.4%), altered bowel habit (n=23; 67.6%), and abdominal pain (n=09; 26.4%). Some patients had more than one symptom. Presenting symptoms in colonic cancer (n=29) were: altered bowel habit (n=24; 82.7%), and abdominal pain (n=16; 55.1%). Some patients had multiple symptoms. Patient's delay (median) in seeing a physician was 08 weeks (range 1–32 weeks) for rectal cancer versus (median) 06 weeks (range 01–364 weeks) for colonic cancers. Time to definitive diagnosis following the first visit to a physician was: rectal cancer (median) 18 weeks (range 01–192 weeks) versus colonic cancer (median) 12 weeks (range 01–32 weeks).

Conclusion: There was an unacceptable delay in time to diagnosis of colorectal cancers from the time of patient first visit to the physician.

207. COMPUTED TOMOGRAPHIC COLOGRAPHY (CTC) FOR COLON CANCER AND POLYP DETECTION

CTC is a new technique allowing minimally invasive imaging of the colon. We are conducting a clinical trial, which has been funded by the North West R&D NHS scheme to determine the accuracy of CTC compared to fibreoptic colonoscopy (FC) in detecting colonic polyps and cancer.

Methods: Patients undergo CTC prior to/on the same day as FC. CTC / FC is performed after standard bowel cleansing/preparation. Two CT acquisitions are performed with the patient supine and then prone using a single spiral CT following administration of intravenous Buscopan and colonic air insufflation. The findings of CTC are correlated with the findings of FC in each patient.

Results: To date 112 patients have been recruited. The FC patient diagnoses were as shown in the table.

FC was completed to the ceacum in only 79% of patients whereas CTC was completed in all. A total of 65 polyps were detected by FC. CTC detected 20 of 22 polyps greater than 1 cm but only 22 of the 43 polyps less than 1 cm in diameter. In addition 5 false positives on CT were identified. 9 cancers seen at FC were all detected by CTC. Additionally CTC detected two further cancers in the right side of the colon not reached at FC and a renal cell carcinoma in a patient presenting with pain and change in bowel habit

Discussion: Initial results show that CTC is a sensitive method of detecting colonic cancers and the majority of polyps > 1 cm. All cancers and 91% of 1cm polyps have been identified by CTC. Up to date figures from this study will be presented.

208. DISTRIBUTION OF COLORECTAL ADENOMAS: CAN FLEXIBLE SIGMOIDOSCOPY BE EFFECTIVE FOR SCREENING?

Screening flexible sigmoidoscopy has the potential to reduce colorectal mortality by detecting polyps followed by colonoscopy and polypectomy. However the effectiveness of flexible sigmoidoscopy depends on the frequency of proximal polyps in the left colon within reach of the flexible sigmoidoscope. We have therefore determined this frequency in our population.

Methods: Consecutive patients were included if at least one colonic polyp was detected during index colonoscopy. These patients were searched from endoscopy databases and hospital diagnostic codes.

Results: 234 patients had at least one polyp at index colonoscopy. Colonoscopy was performed for investigations of lower gastrointestinal symptoms and anaemia. The caecum was intubated in 209 (89%). The mean age was 62 years (range 33–89 years).

199 patients (85%) had at least one adenoma (the rest had hyperplastic polyps or carcinoma). 119 (60%) were male and 80 (40%) were female. 21(11%) subjects had more than two adenomas. There were a total of 269 adenomas of which 195 (72%) were in the rectosigmoid colon. There were 199 “high risk adenomas” (adenomas larger than 10 mm in diameter, adenomas containing villous components, or adenomas with severe dysplasia). 146 (73%) of these were in the rectosigmoid colon. 32 (16%) subjects had adenomas only proximal to the sigmoid colon, including 18 (9%) subjects with “ high risk adenomas”.

Conclusion: 72% of adenomas were within the rectosigmoid colon and could have been detected by flexible sigmoidoscopy. 16% of patients with proximal polyps would have been missed by flexible sigmoidoscopy. These figures support the recommendation of flexible sigmoidoscopy for colorectal cancer screening.

209. RETROPERITONEAL MARGIN TUMOUR INVOLVEMENT IN CAECAL CARCINOMA

Background: Mesorectal plane tumour involvement is a well established predictor of local recurrence in rectal carcinoma. However, the relationship between retroperitoneal surgical margin (RSM) tumour involvement (TI) and local recurrence in caecal carcinoma is poorly characterised.

Aim: To assess the rate of RSM TI in caecal carcinoma and to compare this with the previously published rate of local tumour recurrence.

Methods: 37 right hemicolectomy specimens were studied. During routine specimen dissection, at least one additional tissue block was taken to include the tumour and the RSM. The distance of the tumour from the RSM was measured using a microscope and vernier scale. The Dukes' stage, TNM stage and presence or absence of anterior peritoneal surface (APS) TI was also recorded in each case. RSM and APS TI were defined as the presence of tumour (or an involved lymph node) within 1mm of the RSM and APS respectively.

Results: RSM and APS TI was present in 4 cases (11%) and 26 cases (70%) respectively. Direct (ie non-nodal) RSM TI (2 cases) only occurred in posterior or circumferential tumours.

Conclusion: RSM TI, although less common than APS TI, occurs within a significant number of caecal carcinomas. The rate of RSM TI identified in this study compares favourably with a previously published local recurrence rate of 10% in caecal carcinoma (Ann Surg 2000;232:181–6), suggesting that RSM TI is an important predictor of recurrence in caecal carcinoma. It is possible that patients with RSM TI may benefit from postoperative radiotherapy.

210. LOW INCIDENCE OF COLORECTAL CANCER IN SOUTH ASIANS RESIDENT IN THE UK

Background and aims: Colorectal cancer is relatively uncommon in India. Data from the 1970's showed reduced mortality from colorectal cancer in South Asians in the UK (BMJ 1984;289:1185–7). There have, however, been no large studies of racial differences in colorectal cancer incidence in the UK. Many South Asians have been resident in the West Midlands for several decades. We aimed to determine whether there was a reduced incidence of colorectal cancer in South Asians in Wolverhampton, and whether there were trends in incidence over the past decade.

Methods: Cases of colonic and rectal cancer from 1990–99 were identified from the Histopathology Dept database. South Asian patients were identified by surname/forename analysis, and African and Oriental subjects excluded. Age-sex standardised incidences were calculated using Census data.

Results: From 1990–99 the median age-sex standardised incidence of colonic cancer was 14.69/100,000/year in South Asians compared to 37.20/100,000/year in non-Asians (96% white, 4% black Caribbean) (p=0.0002). For rectal cancer the median age-sex standardised incidence in South Asians was 4.26/100,000/year compared to 22.57/100,000/year in non-Asians (p=0.002). There was a trend towards increasing incidence of colonic cancer from 1990–99 in non-Asians (p=0.03), but no significant trend in Asians. Rectal cancer incidence is increasing in Asians (p=0.049), but not in non-Asians. Standardised Morbidity Ratios for cancer in South Asians is shown in the table.

Conclusions: There is a markedly reduced incidence of colonic and rectal cancers in South Asian immigrants compared to whites and black Caribbeans. The rates of colonic cancer in South Asians have not increased over the last 10 years as might be expected with prolonged exposure possible western environmental factors predisposing to colorectal neoplasia. Rectal cancer is increasing in this group, however.

211. SIGNIFICANCE OF PROXIMAL COLONIC TUMORS IN PATIENTS WITH DISTAL COLONIC POLYPS

Colonic polyps are mainly distal in distribution and proximal polyps are infrequent and associated with low recurrence rate. This audit was designed to assess the distribution of colonic polyps discovered at colonoscopy in symptomatic patients with emphasis on the characteristics of proximal lesions (Proximal to the Splenic flexure) in patients with distal polyps. Two hundred and four polyps were resected endoscopically from 99 patients who presented with altered bowel habits and/or rectal bleeding. There were 58 males and 41 females with a mean age of 65 ±14 (SEM). They had been symptomatic for a mean of 6 ±17 months before undergoing colonoscopy. One hundred and fifty (74%) polyps were resected at the index colonoscopy of which only 13 (9%) polyps were proximal and 137 (91%)were distal. 54 other polyps were resected at subsequent surveillance colonoscopy of which only 9 (17%) were proximal and 45 distal. 83 polyps (41%) showed evidence of high grade dysplasia, 22 (11%) showed low grade dysplasia, in the remaining 99 polyps there was no dysplastic changes. The 22 proximal polyps, 12 (55%) showed high grade dysplasia and 2 (10%) low grade dysplasia as compared to 39% and 11% respectively for distal polyps. There were four colonic cancers diagnosed either at the index colonoscopy (2) or at surveillance colonoscopy (12 and 60 months). All four cancers were Duke A/B and successfully resected.

Conclusions: The majority of advanced colonic tumours are located distally. Proximal lesions constituted less than 10% of all tumours resected but a significant proportion of proximal polyps had high grade dysplasia. This contrasts with distal lesion when high grade dysplasia was evident in just over a third of all specimens.

212. NEO-ADJUVANT THERAPY (NAT) IN RECTAL CANCER: TUMOUR REGRESSION AND IMPACT ON LYMPH NODE HARVEST

Background: Neo-adjuvant therapy is known to cause tumour down staging in rectal cancer. This study evaluated the impact of NAT on tumour regression and lymph node harvest.

Patients and Methods: Twelve patients (6 males; median age-58 years, range 26–72) with rectal cancer were subjected to high dose neo-adjuvant therapy (4500cGY in 25 fractions).Tumour regression (TRG) was graded 1–5. TRG1- no residual tumour cells; TRG2- rare residual tumour cells with marked fibrosis; TRG3-marked fibrosis with scattered tumour cells or groups; TRG4- abundant cancer cells with little fibrosis; TRG5- no tumour regression. Lymph nodes were harvested by dissecting along blood vessels. Data was compared with 10 randomly selected non irradiated controls. (3males, median age 54 years, range 22–65years)

Results: Tumour regression was seen in all patients; 3(25%) had grade 1 regression, 2(17%) had grade 2 regression, 2(17%) had grade 3 and 5(42%) grade 4 regression. Median nodal harvest was 3 (range 0–11) after NAT compared with 9 (range 1–19) in those without NAT (p<0.01, t-test). Median size of the harvested nodes after NAT was 5mm(range 2–10) versus 9mm (range 4–12) without NAT (p<0.01). Tumour deposits were identified in 6 of 44 nodes (14%) after NAT compared with 16 of 93 (17%) nodes without NAT (p>0.05).

Conclusion: Although NAT down stages rectal cancer, it results in a significantly lower lymph node yield which are also significantly smaller in size compared with non irradiated controls. Histopathologists must be aware of this to ensure adequate sampling, and hence accurate reporting of lymph node status in irradiated rectal cancer.

213. 5-HYDROXYTRYPTAMINE (5-HT) LEVELS IN COLONIC MUCOSA IN THE IRRITABLE BOWEL SYNDROME (IBS): ASSESSMENT BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC)

Introduction: We have shown previously by immunohistochemistry an increase in 5-HT staining enterochromaffin cells (EC) in the colonic mucosa of IBS patients.

Aims: To assess any differences between IBS patient and control total colonic mucosal 5-HT levels as quantified by HPLC.

Methods: Eight patients with IBS and 4 control patients with normal colonoscopy for polyps or rectal bleeding had biopsies each taken from the ascending, transverse and sigmoid colon. Immunostaining was performed using the avidin biotin method (Vectastain elite kit) with anti-serotonin (5-HT) mouse monoclonal antibody. Stained cell numbers in five crypts per specimen were assessed using semi-automated image analysis with a KS400 (Zeiss Ltd) system and expressed as mean number of stained cells per unit crypt length (um) + standard error. Samples for HPLC were prepared by homogenising biopsies in 0.5% perchloric acid with 2mM EDTA. Data are expressed as a mean in nmol/mg dry weight(dw) ± standard error. Results were examined by Mann-Whitney analysis. (Significance level at p<0.05).

Results: Immunostaining studies of colonic mucosa showed 1.43 (± 0.16) stained cells per unit crypt length in IBS v 0.89(± 0.15) in controls(p=0.042). However, total mucosal 5-HT by HPLC was higher in controls than IBS (3.05± 0.48 vs 2.21±0.53 nm/mg dw (p=.03)).

Conclusion: These studies show a lower total colonic mucosal 5-HT level in IBS than controls. In contrast higher numbers of 5-HT staining EC cells are seen in IBS than controls. This apparent discordance might be explained by the increased release and consequent depletion of 5-HT from the colonic mucosa in IBS with a compensatory chronic increase in the number of EC cells which would appear not to reflect the total 5-HT concentration since the immunostaining does not quantitate intracellular levels of 5-HT.

214. EFFECTS OF LACTOBACILLUS PLANTARUM 299V ON SYMPTOMS AND COLONIC FERMENTATION IN IRRITABLE BOWEL SYNDROME (IBS)

Introduction: 50% of IBS sufferers may have food intolerances, an abnormal colonic flora and malfermentation. The probiotic Lactobacillus plantarum 299V (Probi AB, Lund, Sweden) has been shown to promote colonic fermentation in healthy volunteers and to improve symptoms in a group of IBS subjects.

Methods: Twelve patients with IBS fulfilling the Rome criteria took part in a double-blind, cross-over 4 week trial of 125mls Lactobacillus plantarum 299V (5x10⁷cfu/ml) daily against a placebo drink of similar colour and taste. Unbeknown to patients and investigators all received placebo first to avoid any cross-over effect of the active preparation. A validated composite symptom score was completed daily. After each treatment fermentation was assessed by 24hrs continuous measurement of gaseous exchange in a 1.4³m canopy followed by breath hydrogen determination for 3 hrs after 20mls of lactulose. Hydrogen was measured by electro-chemical cell (GMI, Renfrew, UK)

Results: No changes were seen in symptoms or calorimetry results (table).

Breath hydrogen excretion after lactulose was reduced by the probiotic (median at 120mins 6ppm; placebo, 17ppm p=0.019).

Conclusion: L. plantarum 299V had a beneficial effect on colonic fermentation reflected in reduced breath hydrogen after lactulose, but not sufficient to reduce total hydrogen production, or to affect patients' symptoms.

215. LACTULOSE HYDROGEN BREATH TEST IN THE DIAGNOSIS OF IRRITABLE BOWEL SYNDROME (IBS) CAUSED BY FOOD INTOLERANCE

Introduction: IBS may be associated with food intolerance, and malfermentation of food residues in the colon leading to excess hydrogen production (Lancet1998;352:1187–9). Malfermentation might provide the basis for a diagnostic test to identify IBS patients suitable for dietary treatment.

Methods: Colonic fermentation, measured by continuous measurement of gaseous exchange over 24hrs in a 1.4³m tent calorimeter, was compared in 18 unselected subjects fulfilling the Rome criteria for IBS, 10 normal volunteers and 12 patients with IBS who had previously failed to respond to an exclusion diet. Immediately after calorimetry, each subject, fasting, received 20gms of lactulose and end expiratory breath samples were collected every 30 minutes for three hours. Hydrogen concentrations in tent gases and breath samples were determined by an electrochemical cell (GMI, Renfrew, UK).

Results: Total 24hr excretion of hydrogen, as in earlier studies, was significantly greater in the IBS group (median 333.7ml/24hrs, IQR 234.7–445.67) compared to the normal volunteers [median 203.1ml/24hrs, IQR 131.4–256 , p= 0.002] or the failed-diet group [median 204.5ml/24hrs, IQR 111.35–289.13 , p= 0.015]. However, no difference was detected in breath excretion of hydrogen following lactulose in any group. Small bowel transit was similar in IBS subjects and controls.

Conclusion: This confirms, in a larger number of patients, our earlier report that total hydrogen production over 24hrs is increased in IBS associated with food intolerance. The lactulose hydrogen breath test, however, does not reflect total 24hr hydrogen production and has no diagnostic value in identifying this subgroup of IBS.

216. COMPARISON OF THE CAECAL AND FAECAL MICROFLORA OF HEALTHY SUBJECTS AND PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS)

Introduction: Colonic malfermentation has been suggested to be a factor producing IBS and IBS patients have been shown to have lower numbers of lactic acid bacteria in their stools with increased aerobe counts. The caecum is the most important colonic region for bacterial fermentation, but it is not known if the faecal flora is representative of that of the caecum.

Methods: 7 subjects referred for investigation of rectal bleeding whose bowel function and colonoscopy were normal, were considered healthy controls. These and 8 IBS patients were prepared for colonoscopy by a single 100ml enema to empty the sigmoid, leaving the proximal colon undisturbed. The colonoscope was then passed to the caecum using CO₂ for insufflation to maintain anaerobic conditions. Caecal fluid was aspirated and mucosal biopsies taken. Patients also provided faecal specimens. Samples were cultured using standard aerobic and anaerobic microbiological techniques. Dry weights of the specimens were obtained by freeze-drying to standardise results.

Results: There were significantly higher numbers of anaerobes in the faeces of healthy subjects compared with IBS patients (P = 0.021). There were no significant differences between numbers of aerobes or lactic acid bacteria (LAB) in the faeces of the two groups. Lower numbers of organisms were detected in lumen samples. There were no significant differences between numbers of anaerobes, aerobes or LAB in the caecal lumens of healthy and IBS subjects. In IBS patients, lactobacilli were present in the caecal mucosae and caecal lumen but were not detectable in the faeces. Aerobes were detected in the caecal mucosae of 5 IBS patients compared with 2 of the healthy subjects (P = 0.072).

Conclusion: Differences in the caecal and faecal flora of may be a factor contributing to colonic malfermentation and the development of IBS.

217. IRRITABLE RECTUM: THE MOST COMMON CAUSE OF FAECAL INCONTINENCE IN A SPECIALIST COLORECTAL PRACTICE

Faecal incontinence (FI) is a common symptom in patients referred to coloproctology and may be due to many causes. We investigate all patients referred with FI. A profile of a consecutive series of these patients is presented. 100 consecutive patients with FI were investigated by ano-rectal physiology, endosonography (USG) and where indicated video proctography. The median age of the patients was 55 years (22–84); 79 were female of whom 44 had an adverse event during childbirth. On investigation the basal anal canal pressure was <60mmHg in 82 patients and <30mmHg in 36. The corresponding maximum squeeze pressure was <100mmHg in 83 patients and <50mmHg in 26. The pudendal terminal latency was prolonged in only 20 patients. Rectal sensitivity was assessed using an intra-rectal balloon: 56 patients were unable to tolerate inflation beyond 50 ml. Sphincter defects were identified on USG in 10 patients (3 of IAS, 1 EAS and 7 both internal and external sphincters). On the basis of both clinical history and investigation the aetiology of the FI was considered to be multi-factorial in 47 patients. The predominant diagnoses were: diffuse pelvic floor weakness 16 patients, sphincter deficit 48, and irritable / hypersensitive rectum 53 patients. 29 patients had no demonstrable abnormality of the pelvic floor or sphincters. These data suggest that the cause of FI is often multi-factorial. In this series hypersensitivity of the rectum was an important and previously unrecognised cause of faecal incontinence. This has important implications for treatment especially if surgery is considered.

218. SMOKING AND ANASTOMOTIC LEAK FOLLOWING ANTERIOR RESECTION OF THE RECTUM

Introduction: Anastomotic leak is a major cause of morbidity and mortality following colonic resection and occurs in 2% to 17% of cases. The level of anastomosis, integrity of blood supply and obesity have previously been considered risk factors for leak.

Methods: Clinical details of all patients undergoing anterior resection of the rectum over a two year period were reviewed.

Results: Two hundred and eight patients (116 male) underwent anterior resection of the rectum. There were 25 combined clinical and radiological leaks (12%). Anastomotic breakdown was significantly associated with a history of smoking (χ²=5.85, 1d.f., p=0.016) or drinking more than 28units of alcohol per week (Fisher's Exact test p=0.03). Smoking, but not alcohol, was found to be independently associated with leak (relative risk 3.1 vs. non-smokers, 95% c.i. 1.2–8.2). The risk of leak was increased for both current smokers and ex-smokers. Male patients and patients undergoing low anterior resection showed a trend towards higher rates of leak whilst the age of the patient, grade of surgeon and type of post-operative analgesia did not significantly affect the risk of leak. Overall 30 day mortality was 12% for patients with an anastomotic leak compared with 5.5% for those without.

Conclusions: Smokers are 3 times as likely to suffer an anastomotic leak following anterior resection of the rectum than non-smokers. Smoking was the strongest independent risk factor studied in this series. The increased risk of leak from smoking is not reduced in patients who have given up for greater than ten years prior to surgery. A history of smoking, past or present, should influence the decision to perform a concurrent defunctioning stoma in patients undergoing an anterior resection of the rectum.

219. EPIDURAL INCREASES INFECTION RATE FOLLOWING LEFT-SIDED COLONIC RESECTION

Background: There is an increasing use of epidural anaesthesia during left-sided colonic resections, it is however unknown if the anaesthetic technique and post operative provision of analgesia influences morbidity. POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) and Portsmouth correction (P-Possum) are accepted as physiological audit tools to predict morbidity and mortality in GI surgery, allowing cross group analysis. In comparing observed to expected morbidity, observed complications are equally weighted between mild and severe.

Methods: A retrospective analysis of 148 patients' consecutive left-sided resections over a 25 month period was undertaken. Analysis of observed complication rate was compared to POSSUM expected morbidity and expected mortality; Portsmouth corrected morbidity and correlation between type of anaesthesia/analgesia was also assessed.

Results: Observed:Expected mortality was 0.359 (P-Possum 1.062), O:E morbidity 1.74. Of these 148 patients, only 15 received PCA. 46.3% of observed morbidity were infective, 82.8% were mild (pyrexia of unknown origin, urinary, chest or line), and 17.2% severe (deep infection or septicaemia). Expected Mortality and Morbidity of patients receiving PCA and Epidural were similar (p=0.343 and p=0.348). A greater infection rate is seen with Epidural (45.1%, 18.4% severe) compared to 20% patients receiving PCA, of which none were severe (χ²: p=0.02). 12.5% patients receiving Epidurals experienced hypotension (systolic <90mmHg for >2hrs), and of these 58.9% had septic episodes (p=0.053).

Conclusions: In patients undergoing left-sided colonic resection, patients receiving epidural analgesia were more than twice as likely to experience an infective adverse event as those receiving PCA. This may in part be due to hypotensive episodes associated with epidural.

220. USE OF WHOLE CRYPT MOUNTS TO QUANTIFY APOPTOSIS IN HUMAN COLONIC CRYPTS EXPOSED TO IONISING RADIATION OR DIETARY INTERVENTION WITH FISH OIL

In healthy colonic mucosa a balance is maintained between cell production and loss via apoptosis or exfoliation. Crypt cell apoptosis is a relatively rare event, but is essential for deletion of DNA-damaged cells from the crypts. Having previously shown that dietary intervention with fish oil can increase crypt cell apoptosis in rat intestine (Carcinogenesis 20:645–50), we have quantified apoptosis in the distal colons of cancer patients who received either a placebo or fish oil immediately before surgery, and compared the results with the effects of preoperative radiotherapy.

Methods: Samples of colonic mucosa (5, 10, 15, 20 and 25cm from the tumour) were taken from the resected tissue of patients (n=7) diagnosed with left-sided colon carcinoma, who had received X-ray therapy (25Gy in 5 fractions over 5 days) before surgery. Patients with a similar diagnosis, not requiring pre-operative radiotherapy, were randomly assigned to receive fish oil capsules (n=25; 2.4g n-3 fatty acids/day) or a placebo (n=24) for 7–21 days pre-operatively. All tissue samples were immediately transferred to fixative for storage. Following rehydration and staining with Feulgens reagent, whole crypt mounts were prepared to assess mitosis and apoptosis, using morphological criteria.

Results: In the irradiated intestine, crypt structure was extremely delicate within a 10cm radius of the tumour and cells were severely damaged with massive DNA fragmentation. Further from the tumour site crypts retained their normal morphology but those from irradiated mucosa had a significantly lower mitotic rate and a higher frequency of apoptosis than the controls. The frequency of apoptosis was inversely proportional to distance from the site of the tumour. There was no effect of fish oil on apoptosis in patients not receiving radiotherapy.

Conclusions: The whole crypt mount technique can be used to visualise and quantify apoptosis in human intestinal mucosa, and to assess the effects of dietary or other interventions.