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Aim Patients with unfavourable pathology after transanal endoscopic microsurgery (TEM) should be offered completion surgery (CS) if appropriate. The aim of this retrospective cohort study was to assess the short-term outcome and long-term oncological results of CS and identify factors compromising the quality of resection specimens. Method Data were retrieved and analysed on patients who underwent CS from a comprehensive national TEM database (1992–2008) and the institutional prospective database from the Oxford University Hospitals (2008–2011). Results There were 36 patients eligible for analysis. Postoperative complications occurred in 19 and were minor (grade I–II) in 13 and major (grade III–V) in six patients. The quality of the resected specimen was graded as good in 23 (64%), moderate in six (16.6%) and poor in seven (19.4%). Full-thickness excision by TEM (P = 0.03), an interval to CS greater than 7 weeks (P = 0.05) and distally located lesions (P = 0.04) were associated with increased risk for an inferior surgical specimen. Overall survival after CS was 91% at 1 year and 83% at 5 years. Patients with a ‘good’ TME specimen had significantly improved disease-free survival compared with patients with an ‘inferior’ specimen (100 vs 51%, P = 0.001). Conclusion Patients having full-thickness TEM excision, distally placed lesions and a long interval (> 7 weeks) to CS were likely to have an inferior TME specimen. The results confirm that CS after TEM does not negatively influence local recurrence and survival, but the reduced disease-free survival in patients with an inferior specimen is of concern.

Aim Rectal prolapse is a profoundly disabling condition, occurring mainly in elderly and parous women. There is no accepted standard surgical treatment, with previous studies limited in methodological quality and size. PROSPER aimed to address these deficiencies by comparing the relative merits of different procedures. Method In a pragmatic, factorial (2 × 2) design trial, patients could be randomised between abdominal and perineal surgery (i), and suture vs resection rectopexy for those receiving an abdominal procedure (ii) or Altemeier's vs Delorme's for those receiving a perineal procedure (iii). Primary outcome measures were recurrence of the prolapse, incontinence, bowel function and quality of life scores (Vaizey, bowel thermometer and EQ-5D) measured up to 3 years. Results Two hundred and ninety-three patients were recruited: 49 were randomised between surgical approaches (i); 78 between abdominal procedures (ii); and 213 between perineal procedures (iii). Recurrence rates were higher than anticipated, but not significantly different in any comparison: Altemeier's vs Delorme's 24/102 (24%) and 31/99 (31%) [hazard ratio (HR) 0.81; 95% CI 0.47, 1.38; P = 0.4]; resection vs suture rectopexy 4/32 (13%) and 9/35 (26%) (HR 0.45; 95% CI 0.14, 1.46; P = 0.2); perineal vs abdominal 5/25 (20%) and 5/19 (26%) (HR 0.83; 95% CI 0.24, 2.86; P = 0.8). Vaizey, bowel thermometer and EQ-5D scores were not significantly different in any of the comparisons. Conclusion No significant differences were seen in any of the randomised comparisons, although substantial improvements from baseline in quality of life were noted following all procedures.

Objective The current evidence for fibrin glue as a treatment for anal fistulae is mixed. This study reviews the experience of fibrin glue as a treatment for anal fistulae in a single tertiary referral centre and attempts to identify factors related to failure of therapy and the length of follow-up required. Method Patients with fistulae in ano that were treated with fibrin glue between February 2004 and August 2008 were analysed. All procedures were performed by two colorectal consultants based at the Queens Medical Centre, Nottingham. All patients were followed-up to assess the outcome of this treatment. Results Forty patients (21 male, 19 female) with a mean age of 46.5 years were studied. The mean duration of symptoms prior to presentation was 39 months (range 4–240 months). Presenting symptoms included perianal discharge (72.5%), perianal abscess (57.5%), pain (12.5%), PR bleeding (7.5%), itching (5%) and urgency (2.5%). Patients had a minimum of two follow-up appointments and the median follow-up period was 5.2 months (range 1–16 months). Following MRI and operative assessment, 28 (70%) of the 40 fistulae were considered complex (high trans-sphincteric, extra-sphincteric, pouch-vaginal). Patients who had inflammatory bowel disease were classified as simple tracts but all failed to heal (three patients). Twenty of the complex fistulae failed to heal. Three patients who had repeat application of glue for their complex fistulae failed to heal on follow-up. Of the remaining 12 patients who had simple fistulae in ano, five (41.7%) healed completely. There were no complications such as abscess, related to treatment. All patients who were asymptomatic at 3 months did not develop any further recurrence. Conclusion Fibrin glue is a simple treatment strategy, preserves sphincter function with minimal adverse side effects. It should therefore be considered as possible first line treatment in simple fistulae but it is less likely to be successful in complex or those fistulae associated with inflammatory bowel disease. Repeat gluing is unlikely to be successful. Fistulae that have failed to heal by 3 months will need further treatment.

Background & Aims: Although observational studies have found regular aspirin use to be associated with a reduced risk of colorectal neoplasia, results from randomized trials using aspirin have been inconsistent. Dietary folate intake also has been found to be associated with a reduced risk of colorectal neoplasms in observational studies. Methods: A multicenter, randomized, double-blind trial of aspirin (300 mg/day) and folate supplements (0.5 mg/day) to prevent colorectal adenoma recurrence was performed using a 2 × 2 factorial design. All patients had an adenoma (≥0.5 cm) removed in the 6 months before recruitment and were followed-up at 4-month intervals with a second colonoscopy after approximately 3 years. The primary outcome measure was a colorectal adenoma diagnosed after baseline. Results: A total of 945 patients were recruited into the study, of whom 853 (90.3%) underwent a second colonoscopy. In total, 99 (22.8%) of 434 patients receiving aspirin had a recurrent adenoma compared with 121 (28.9%) of 419 patients receiving placebo (relative risk, 0.79; 95% confidence interval [CI], 0.63–0.99). A total of 104 patients developed an advanced colorectal adenoma; 41 (9.4%) of these were in the aspirin group and 63 (15.0%) were in the placebo group (relative risk, 0.63; 95% CI, 0.43–0.91). Folate supplementation was found to have no effect on adenoma recurrence (relative risk, 1.07; 95% CI, 0.85–1.34). Conclusions: Aspirin (300 mg/day) but not folate (0.5 mg/day) use was found to reduce the risk of colorectal adenoma recurrence, with evidence that aspirin could have a significant role in preventing the development of advanced lesions.

Purpose: The UDP glucuronosyltransferase 1A6 (UGT1A6) and cytochrome P450 2C9 (CYP2C9) enzymes participate in the metabolism of nonsteroidal anti-inflammatory drugs, endogenous substances, and carcinogens. Functional polymorphisms of UGT1A6 (T181A and R184S) and CYP2C9 (R144C and I359L) have been reported to modify the protective effect of aspirin on colorectal adenoma risk. We aimed to further investigate the effect of these genetic variants on the development of colorectal neoplasia. Experimental Design: We examined the relationship between UGT1A6 and CYP2C9 genotype and colorectal adenoma recurrence in 546 patients participating in a randomized placebo-controlled aspirin intervention trial. Results: Although colorectal adenoma recurrence was not significantly influenced by CYP2C9 genotype, carriers of variant UGT1A6 alleles were at significantly reduced risk of colorectal neoplasia recurrence [relative risk (RR), 0.68; 95% confidence interval (95% CI), 0.52-0.89]. This risk reduction was also evident when the analysis was confined to advanced neoplasia recurrence (RR, 0.71; 95% CI, 0.47-1.09). When patients were stratified by genotype and aspirin intervention, those with variant UGT1A6 alleles were at reduced recurrence risk irrespective of whether they received aspirin or placebo (RR, 0.62; 95% CI, 0.42-0.92 and RR, 0.63; 95% CI, 0.44-0.91, respectively). Conclusions: These findings confirm that UGT1A6 variants influence colorectal carcinogenesis independent of aspirin intake and suggest that they may have clinical value in secondary prevention programs for patients diagnosed with colorectal adenoma.

The use of specialized imaging to assess cryptogenic fistula-in-ano is selective, aimed at delineation of the site of the internal fistula opening and the relationship of the primary and secondary tracks and collections to the main levator plate. Advanced imaging also permits definition of the destructive effects of perirectal sepsis (e.g. internal or external anal sphincter damage, perineal body destruction and an ano- or rectovaginal fistula), which may require secondary reconstructive surgery.We performed a PubMed search of outcomes for fistula management in the English and non-English literature, and summarized results regarding the accuracy of internal opening and horseshoe detection as well as the operative correlation for cryptogenic and non-cryptogenic fistula-in-ano using endoanal ultrasound (EAUS) and magnetic resonance (MR) imaging. Only literature defining these characteristics was included.The advantages and limitations of the main forms of imaging are discussed in this review with emphasis on EAUS and endoanal or pelvic phased-array MR fistulography. The new technique of transperineal sonography is highlighted. A small but important group of patients with complex fistula-in-ano require specialized imaging. There are specific limitations of endoanal ultrasound (EAUS) which necessitate pelvic phased-array MR imaging. Initial work suggests that EAUS may have a role in intraoperative use for image-guided drainage of recurrent abscesses where operative interpretation can be difficult. The coloproctologist in a tertiary referral center must acquire the skills of ultrasound performance in order to successfully treat fistulous disease, suggesting a role for formal imaging accreditation as part of coloproctological training.Future studies should determine both what sequential imaging algorithms for imaging are cost-effective as well as predictive of fistula cure.

PURPOSE: The management of high fistula-in-ano presents a difficult surgical challenge. Laying open of high transsphincteric, intersphincteric, and suprasphincteric fistulas is associated with incontinence. Mucosal advancement flap can be technically difficult and is associated with ectropion and incontinence. We report a new technique for the treatment of fistulas, which may eliminate these problems. PATIENTS AND METHODS: Between 1997 and 2002, 18 patients (13 males), median age 46 (range, 25–64) years with high fistula-in-ano were treated. There were ten transsphincteric, four intersphincteric, and four suprasphincteric fistulas. In all patients, perianal sepsis was allowed to resolve completely with a drainage seton before definitive surgery. The surgical technique used involved core fistulectomy, curettage of any cavity, closure of the defect in the internal anal sphincter, and a V-Y advancement buttock flap to cover the internal opening, leaving the site of the external opening for drainage while preserving both internal and external sphincters. Outcome was assessed in terms of healing and continence. RESULTS: Most patients were discharged from the hospital within 48 hours. Median follow-up was 19 (range, 3–60) months. There were three patients who failed to heal. Of these, two underwent repeat surgery and healed. Two further patients had recurrent fistulas, both of whom continued with conservative treatment. Overall, 15 of 18 (83 percent) patients experienced healing of their fistula. Continence was preserved in all patients. CONCLUSION: This procedure is easy to perform, healing is rapid, and it appears to be effective in curing fistula-in-ano while preserving both external and internal anal sphincters.

AIMS To determine the harm that ensues from faecal occult blood (FOB) screening for colorectal cancer. METHODS 150 251 people were randomly allocated either to receive biennial Haemoccult FOB tests (n =75 253) or not to be contacted (n=74 998). Study group patients returning positive tests were offered colonic investigation; 1774 underwent complete investigation of the colon. RESULTS There was no significant difference in the stage at presentation of interval versus control group cancers. Survival in the interval cancer group was significantly prolonged compared with the control group. Sensitivity for colonoscopy or flexible sigmoidoscopy and double contrast barium enema (DCBE) was 96.7%. There were no complications of DCBE but seven (0.5%) complications of colonoscopy, of which six required surgical intervention. There were no colonoscopy related deaths. No patients without colorectal cancer died within 30 days of colonic investigation. Five patients died within 30 days of surgery for screen detected colorectal neoplasia and a further two died without having surgery. Six patients died after 30 days but within two years of surgery for screen detected benign adenomas or stage A cancers; in all cases the cause of death was not related to colorectal cancer. CONCLUSIONS There was investigation related morbidity but no mortality and little to support overdiagnosis bias. The group returning falsely negative tests had a better outcome compared with the whole control group. There is a negative side to any screening programme but mortality reduction in this and other trials suggests that a national programme of colorectal cancer screening should be given consideration.

Evidence as to the value of preoperative carcinoembryonic antigen (CEA) in guiding treatment for patients with colorectal cancer is conflicting. The aim of this prospective study was to investigate the value of preoperative CEA in predicting tumour factors of proven prognostic value and long-term survival in patients undergoing surgery for colorectal cancer. Preoperative serum CEA, tumour ploidy, stage and grade were ascertained in 277 patients undergoing colorectal cancer surgery. This cohort of patients were followed up for a minimum of 5 years, or until death, in a dedicated colorectal clinic. Patients with an elevated CEA had a 5 year survival of 39%. This increased to 57% if the CEA was normal (P=0.001). The proportion of patients with a raised CEA increased with a more advanced tumour stage (P < 0.000001) and a poorly differentiated tumour grade (P < 0.005). Once stage had been controlled for, CEA was not a predictor of survival. No relationship between tumour ploidy and CEA was found. In conclusion, a raised preoperative serum CEA is likely to be associated with advanced tumour stage and poor long-term survival, compared with patients with a normal value.

Background—The risk of colorectal cancer is higher among relatives of those affected. The neoplastic yield reported from screening such individuals varies enormously between studies and depends on the age and strength of the family history of those screened.Aims—To ascertain the neoplastic yield of endoscopic screening of first degree relatives of patients with colorectal cancer by age and familial risk.Subjects—A total of 330 individuals with a family history of colorectal cancer.Method—Endoscopic screening conducted according to a protocol.Results—Adenomas were found in 12%, and adenomas larger than 1 cm in 8%, of “high risk” individuals screened primarily by colonoscopy. Of those with neoplasia, 26% had lesions at or proximal to the splenic flexure. Neoplasia was found in 9.5% of individuals at lower familial risk, screened primarily by 60 cm flexible sigmoidoscopy, 4% of whom had neoplasia larger than 1 cm in size or cancer. Neoplastic yield was greatest in the fourth and fifth decades in those at highest risk, but increased with age in those at lower risk.Conclusions—For individuals with two or more first degree relatives, or relatives who have developed colorectal cancer at a young age, colonoscopy appears to be the only satisfactory method of screening, but 60 cm flexible sigmoidoscopy may be useful in those at lower levels of risk.

Background. Retrospective studies have suggested that DNA tumor content (ploidy) has a significant effect on survival. This group has reported, prospectively, that among patients who had colorectal resections for carcinoma, the 2-year tumor recurrence rate was significantly greater for patients with aneuploid tumor than for those with diploid tumors. This paper reports the 5-year survival rates of this cohort of patients. Methods. Three hundred sixty-three patients who had colorectal resections for cancer between November, 1982, and March, 1988, were studied prospectively. The DNA tumor ploidy was measured from fresh and paraffin embedded tissues. These patients were followed regularly in a dedicated colorectal clinic for a minimum of 5 years or until death. Of the 363 patients studied, 2 were lost to follow-up. Results. Forty percent of the tumors were diploid, the remainder aneuploid. The 5-year survival for patients who had curative resections was 76% for those with diploid tumors compared with 64% for aneuploid tumors (P = 0.05 ; Mantel-Cox, 3.7). On further analysis, the survival benefit conferred by a diploid tumor appeared to be confined to those with Stage B tumors. There was no relation between ploidy and sex, age of patient, stage, histologic grade, or site of tumor. Conclusions. Ploidy is a useful objective measurement of the aggressiveness of Stage B tumors. Patients with aneuploid Stage B tumors have a poor prognosis ; this group may benefit from adjuvant therapy

Genetic changes are important in the development of colorectal cancer. Ploidy and rectal mucosal proliferation were measured in histologically normal rectal mucosa of 85 individuals (mean age 59 years, range 29-74) who had a total colonoscopy. Fifty-one subjects had an adenoma or were undergoing adenoma surveillance. Twenty-two subjects had a strong family history of colorectal cancer and 12 individuals comprised a control group who had a normal colonoscopy without a family history of colorectal cancer. An abnormal DNA content (aneuploidy) was found in the normal mucosa of nine (10.6%) individuals. There was no significant difference in rectal mucosal proliferation with those who had aneuploidy and those who had diploidy. There was a trend towards increased proliferation in those with aneuploidy and adenomas, compared with controls. Of the 35 individuals undergoing adenoma surveillance, eight had recurrent adenomas, and three of these expressed aneuploidy. In the other 27, in whom no adenomas were found, no individual expressed aneuploidy (P = 0.01, Fisher's exact test). Aneuploidy within histologically normal mucosa is an unusual feature, which requires further investigation, particularly in patients developing adenomas.

Rectal mucosal proliferation was measured in 116 individuals using the metaphase arrest technique crypt cell production rate (CCPR). CCPR was found to be significantly elevated in individuals with adenomas (n = 42, CCPR = 13 cc c-1h-1, range 7-25 Cl 10-15) compared with normals (n = 21, CCPR = 10 cc c-1h-1 range 5-24 Cl 7-11, Mann-Whitney P = 0.001 z = 3.2). Mucosal proliferation was increased among individuals who were undergoing adenoma follow up but in whom no further adenomas were found (n = 37 CCPR = 12 range 5-26 cc c-1h-1 Cl 10-14) compared to controls (Mann-Whitney P = 0.01 z = 2.4) Proliferation in vegetarians i.e. low risk (n = 16) was similar to controls. Measurement of proliferative indices in rectal mucosa by the stathmokinetic technique CCPR can discriminate between high and low risk groups for colorectal cancer.

Ninety-seven patients underwent Hartmann's procedure between 1981 and 1986 at the University Hospital, Nottingham. Sixty-one (63%) required this operation as an emergency procedure. There was an overall mortality of 22% and the morbidity rate was 56%. Infective and cardiovascular problems accounted for 77% of all complications encountered reflecting the age and underlying condition ofthe patients requiring this procedure. Thirty patients had successful restoration of intestinal continuity, the majority of these having their original procedure performed as an emergency for benign disease. There were no immediate postoperative deaths from reanastomosis and few short- or long-term anastomotic problems, however there was again considerable postoperative morbidity.

Tumor cell DNA (ploidy) content was measured prospectively in samples from 320 patients resected for colorectal cancer with a minimum follow-up time of 2 years. All patients were followed and those with recurrence were investigated carefully. There was no correlation between tumors with an abnormal cellular DNA content (aneuploid or tetraploid) and patient age, sex, tumor site, pathologic stage, or histologic grade. In 236 patients who underwent potentially curative operations, 75 (32%) had local and/or distant recurrence. The recurrence rate was significantly higher (test statistic, 4.3; P = 0.04) for those patients with aneuploid tumors (52 of 142, 37%) compared with those with diploid tumors (23 of 94, 24%). The subgroups of patients where ploidy exerted an effect were in patients with Stage B tumors or mobile tumors and in patients over 65 years of age. Further analysis showed that there was a twofold increase in local recurrence and a threefold increase in distant recurrence in patients with aneuploid tumors, but no excess of patients who had both local and distant recurrence. Measurement of DNA ploidy can identify a group of patients undergoing curative surgery for colorectal cancer at high risk for recurrence. In combination with clinicopathologic factors, DNA ploidy may be useful in analyzing the results of trials and in planning adjuvant therapy.

There is considerable evidence that most colorectal carcinomas arise in preexisting adenomas. It also appears that there may be a considerable influence of diet in the genesis and growth of adenomas. This evidence is discussed and the current dietary intervention studies in humans are reviewed.

We have investigated the influence of tumour cell DNA content (ploidy) on survival of 416 patients undergoing excisional surgery for colorectal cancer. Two hundred and eleven (51%) tumours had an abnormal DNA content (aneuploid or tetraploid). There was no correlation between ploidy status, sex, age and pathological stage, histological grade, tumour site, local tumour extension or assessment of curability. Patients with tumours with an abnormal DNA content had a poorer survival 68/211 (32%) than patients with near normal (diploid) DNA content 88/205 (43%) (test statistic 5.0, P = 0.02). The patient subgroups in which DNA content exerted an influence on survival were: stage B tumours (P = 0.0058), moderately differentiated tumours (P = 0.004), rectal tumours (P = 0.02), and mobile tumours (P = 0.02). Multivariant analysis showed that pathological stage, local tumour extension and DNA ploidy were all independent prognostic indicators whereas histological grade, tumour site and assessment of 'curability' were not. The influence of pathological stage, however, was much greater than that of local tumor extension or DNA ploidy. Tumour cell DNA content together with pathological stage and local tumour extension may be used in a prognostic index and may be important in planning adjuvant therapy.

BACKGROUND: People with a family history of colorectal cancer have an increased risk of the disease themselves. Many centres are advocating family history screening by endoscopy. AIMS: The performance of chemical and immunological faecal occult blood tests (Haemoccult and Hemeselect) in 212 subjects with a family history of colorectal cancer was assessed. RESULTS: Both Hemeselect and Haemoccult were positive in the only patient with colorectal cancer. Hemeselect was more sensitive than Haemoccult for adenomas (40% compared with 20%) (adenomas larger than 1 cm 75% compared with 50%). No additional abnormality was detected by the addition of Haemoccult or Hemeselect to 60 cm flexible sigmoidoscopy in screening people at lower levels of familial risk. A false positive rate of 16% for Hemeselect resulted in a high proportion of additional colonoscopies in this group. CONCLUSIONS: At present faecal occult blood tests are not sufficiently sensitive or specific to replace endoscopy in screening people at risk of familial colorectal cancer.

INTRODUCTION: Parastomal hernia is a common complication of stoma construction. Although the majority of patients are asymptomatic, about 10% require surgical correction. AIMS: We describe a new surgical approach for the repair of parastomal hernias, which avoids both the need for laparotomy and stoma mobilization. PATIENTS AND METHODS: Nine patients (4 female) with parastomal hernia underwent surgical repair. Median age was 55 years (range 38-73 years). There were 8 para-ileostomy herniae and one paracolostomy hernia. A lateral incision was made approximately 10 cm from the stoma, and carried down to the rectus sheath. The dissection was carried medially towards the stoma, and around the defect in the abdominal musculature. The hernia sac was excised when possible and the fascial defect closed with non-absorbable, monofilament suture. A polyprolene mesh was placed round the stoma by making a slit in the mesh. The skin was closed with subcuticular monofilament absorbable suture. RESULTS: All patients returned to normal diet on the first postoperative day, and were discharged from hospital within 72 h. There were no wound infections, and no recurrences after a median follow up of 6 months (range 3-12 months). DISCUSSION: The technique we describe is simple and avoids the need of laparotomy. The mucocutaneous junction of the stoma is not disturbed, reducing the risk of contamination of the mesh, stenosis or retraction of the stoma. Grooving of the stoma and difficulty in fitting appliances is avoided because the wound is not placed near the mucocutaneous junction. This approach may be superior to other mesh repairs for parastomal hernia.

BACKGROUND AND AIMS—In the USA and many other countries, endoscopic surveillance of colorectal adenoma patients is now widely practised. However, the optimal frequency and mode of such surveillance are not yet established. The aim of this trial was to compare surveillance at one, two, or five year intervals using either flexible sigmoidoscopy or colonoscopy. METHODS—Analysis of a randomised trial of flexible sigmoidoscopy and colonoscopy over one, two, or five years after stratification for "high" or "low" risk of recurrent adenomas. The trial started in 1984. RESULTS—A total of 776 patients were stratified into "high" (n=307) and "low" (n=469) recurrence risk groups and randomised to flexible sigmoidoscopy or colonoscopy at varying intervals. Only 81 recurrent adenomas (30/81 were >1 cm in diameter) were detected in the 2307 person years of follow up within the surveillance study. Adenoma recurrence was significantly higher in the high risk group (relative rate 1.82; 95% confidence interval 1.2-2.9) but recurrence rates per 1000 person years were low and not significantly different in those surveyed by colonoscopy or flexible sigmoidoscopy. Loss to follow up was greatest in those having an annual examination compared with two or five yearly surveillance examinations. Despite surveillance, invasive cancer developed in four patients compared with an expected value of 9.12 for the general population in England (p=0.10); of these four patients who developed cancers, only one was detected by surveillance examination. CONCLUSIONS—Adenoma recurrence rates were much lower than expected in both high and low risk groups. This suggests that endoscopic surveillance should be targeted at high risk groups. A surveillance interval of five years was as effective as shorter intervals in terms of cancer prevention, and was associated with similar compliance to two yearly examinations. Keywords: adenoma; polyp; colorectal cancer; surveillance; colonoscopy

Over a 28-month period, 100 transanal endoscopic microsurgical excisions of rectal tumours were carried out in three centres. The histological diagnosis was benign adenoma in 77 and invasive adenocarcinoma in 23. Complete excision of the tumour with histological confirmation was achieved in 70 (91 per cent) of the adenomas and in all but one of the carcinomas. Of the carcinomas, 18 were recognized before operation and the remaining five were diagnosed on postoperative histology. Of the patients with carcinoma, one had immediate further surgery, nine had radiotherapy and 13 had no extra treatment. To date, four patients have had a recurrence of villous adenoma, and two of the patients treated for invasive carcinoma have had local recurrence. These initial results of transanal endoscopic microsurgery in the UK compare well with those of earlier reports, indicating that the technique has a useful place in the management of sessile adenomas of the mid and upper third of the rectum, and of some carefully selected carcinomas.

Retrospective studies have suggested that DNA tumor content (ploidy) has a significant effect on survival. This group has reported, prospectively, that among patients who had colorectal resections for carcinoma, the 2-year tumor recurrence rate was significantly greater for patients with aneuploid tumor than for those with diploid tumors. This paper reports the 5-year survival rates of this cohort of patients.Three hundred sixty-three patients who had colorectal resections for cancer between November, 1982, and March, 1988, were studied prospectively. The DNA tumor ploidy was measured from fresh and paraffin embedded tissues. These patients were followed regularly in a dedicated colorectal clinic for a minimum of 5 years or until death. Of the 363 patients studied, 2 were lost to follow-up.Forty percent of the tumors were diploid, the remainder aneuploid. The 5-year survival for patients who had curative resections was 76% for those with diploid tumors compared with 64% for aneuploid tumors (P = 0.05; Mantel-Cox, 3.7). On further analysis, the survival benefit conferred by a diploid tumor appeared to be confined to those with Stage B tumors. There was no relation between ploidy and sex, age of patient, stage, histologic grade, or site of tumor.Ploidy is a useful objective measurement of the aggressiveness of Stage B tumors. Patients with aneuploid Stage B tumors have a poor prognosis; this group may benefit from adjuvant therapy.

Seventy-nine patients with colorectal adenomata were randomised to receive calcium carbonate (3,000 mg) or placebo in a double-blind randomised trial to assess the short- and long-term effects on rectal mucosal proliferation measured by the in vitro metaphase arrest technique crypt cell production rate (CCPR). There was no significant difference in mean CCPR between the groups before treatment or after 3 or 12 months. In those patients randomised to calcium, CCPR fell at both 3 months [9.0 (2.8) cc c-1 h-1, t = 3.15, d.f = 76, P = 0.002] and 12 months [9.2 (3.3) cc c-1 h-1 t = 2.7, d.f. = 74, P = 0.009] compared with pretreatment CCPR [12.2 (5.5) cc c-1 h-1]. We have demonstrated that calcium had no effect on mucosal proliferation compared with placebo. The results on adenoma formation are awaited.

Symptoms referrable to large bowel cancer are common, can be seen in other colorectal disorders and are often ignored by patients.

In a single-blind study 38 individuals at increased risk of developing colorectal cancer because of a family history of the disease were randomized to take 10.5 g wheat fibre (Trifyba) or 60 ml lactulose daily for 12 weeks. Rectal biopsies were taken before and after treatment and rectal mucosal proliferation was measured by the crypt cell production rate (CCPR). The mean(s.d.) CCPR was significantly lower in those taking wheat fibre after 12 weeks (7.2(3.4) crypt cells per crypt per h) compared both with values obtained before treatment with wheat fibre (10.2(5.1) crypt cells per crypt per h; P=0.02) and after treatment with lactulose (9.4(3.8) crypt cells per crypt per h; P=0.05). Proliferation in the lactulose group was not significantly different at 12 weeks compared with the value obtained before treatment. This study confirms an anti-proliferative effect of wheat fibre in a group of high-risk individuals.

This study examined the effect of blood transfusion on the prognosis of patients undergoing surgery for colorectal cancer.Potentially curative resections for colorectal cancer were performed in 266 patients who were followed prospectively, with a minimum follow-up of 41 months. They were divided into transfused (n = 121) and nontransfused (n = 145) groups according to their perioperative blood transfusion requirements.There were significantly more rectal tumors (chi 2 = 9.5, df = 1, P = 0.002) and fixed tumors (chi 2 = 4.5, df = 1, P = 0.03) in the transfused group. There was no statistically significant difference between the two groups with regard to recurrence-free survival (chi 2 = 1.1, df = 1, P = 0.3) and overall survival (chi 2 = 2.8, df = 1, P = 0.09).In this study we have found no statistically significant effect of perioperative blood transfusion on the prognosis of colorectal cancer patients.

The in vitro metaphase arrest technique (crypt cell production rate-CPPR) has been used to measure human rectal mucosal proliferation. Study of preincubation times, dose response curves and lag phases suggest that a concentration of vincristine of 5 micrograms/ml and 16 hour preincubation with time point increments between 25 and 125 minutes give optimal conditions for measuring rectal mucosal proliferation. Twenty individuals had rectal CCPR repeated without intervention of any kind. Close correlation was found between the two values (r = 0.89 and P = 0.0001). The effect of polyethylene glycol bowel preparation was also studied in 35 subjects. There was good correlation (r = 0.66, P = 0.007). There was close correlation between rectal and caecal CCPR as measured in 20 patients who had colonoscopy (r = 0.72, P = 0.0003). The in vitro metaphase arrest technique is a useful parameter of rectal mucosal proliferation and may be used with confidence in a number of different clinical situations.

A case of Crohn's colitis with mural bridging lesions is described. The bridging lesions comprised colonic-type mucosa, smooth muscle, nerve fibers, with foci of adipose tissue and fibrous connective tissue. The lesions arose from the muscularis propria proximal to colonic strictures and possibly due to diverticular outpouching of the colonic wall associated with increased intraluminal pressure, although the exact mechanism of their formation appears unclear. This entity has not been previously described in inflammatory bowel disease, to our knowledge. Bridging pseudopolyps are seen in ulcerative colitis and rarely in Crohn's disease but do not contain substantial amounts of smooth muscle and/or nerve fibers. We believe that the mural bridges described in this article represent residual muscularis propria at the site of diverticular formation due to long-standing Crohn's colitis. We speculate that the stricture formation seen distal to the site of the mural bridging lesions may have been an important factor in formation of the colonic diverticula and, hence, these lesions that we interpret as representing residual muscularis propria adjacent to sites of diverticular formation in long-standing Crohn's colitis.

Thirty-seven individuals with an increased lifetime risk of colorectal cancer because of family history and a control group (n = 21) with no such family history underwent colonoscopy. No neoplastic lesion was found in any individual. Rectal biopsies of macroscopically normal mucosa were taken 8 cm from the anal margin and mucosal proliferation assessed by the crypt cell production rate (CCPR). There was no difference in CCPR between the control group (median 10 (95 per cent confidence interval 7–11) cells per crypt per h) and those at intermediate risk (lifetime risk between 1:17 and 1:10, n = 14). However, there was a significant difference in CCPR between the control group and those at higher risk (lifetime risk > 1:10, n = 23) (median CCPR 13 (95 per cent confidence interval 10–17) cells per crypt per h, P = 0·004). A high risk of colorectal cancer derived from family history correlates with an increased colorectal mucosal proliferation rate.

Tumor cell DNA (ploidy) content was measured prospectively in samples from 320 patients resected for colorectal cancer with a minimum follow-up time of 2 years. All patients were followed and those with recurrence were investigated carefully. There was no correlation between tumors with an abnormal cellular DNA content (aneuploid or tetraploid) and patient age, sex, tumor site, pathologic stage, or histologic grade. In 236 patients who underwent potentially curative operations, 75 (32%) had local and/or distant recurrence. The recurrence rate was significantly higher (test statistic, 4.3; P = 0.04) for those patients with aneuploid tumors (52 of 142, 37%) compared with those with diploid tumors (23 of 94, 24%). The subgroups of patients where ploidy exerted an effect were in patients with Stage B tumors or mobile tumors and in patients over 65 years of age. Further analysis showed that there was a twofold increase in local recurrence and a threefold increase in distant recurrence in patients with aneuploid tumors, but no excess of patients who had both local and distant recurrence. Measurement of DNA ploidy can identify a group of patients undergoing curative surgery for colorectal cancer at high risk for recurrence. In combination with clinicopathologic factors, DNA ploidy may be useful in analyzing the results of trials and in planning adjuvant therapy.

Anal fissure is often treated surgically by sphincterotomy. There is growing concern over the effects of this procedure on continence. Nitric oxide donors such as glyceryl trinitrate are thought to cause a reversible ‘chemical sphincterotomy’, capable of healing the fissure. Twenty-one consecutive patients with chronic anal fissure (13 women, mean age 36 years) were treated for 4–6 weeks with 0·2 per cent glyceryl trinitrate ointment applied to the fissure twice daily. Maximum anal resting pressure (MARP) was measured before and after application of the ointment at the first visit. There were 16 posterior and five anterior fissures. Mean(s.d.) MARP fell from 118·7(45·0) to 70·3(34·1) cmH2O over 20 min after application of the ointment (P

Primary aortoenteric fistula is rare. The most common cause is atherosclerosis, followed by infection and carcinoma of the head of the pancreas. A case of spontaneous aortojejunal fistula due to recurrent colorectal cancer is reported.

The expression of Le(y) (Lewis(y) Hapten), a difucosylated type 2 blood group-related antigen, in colorectal lesions was studied by using the monoclonal antibody C14. In normal colonic mucosa, strong staining has been observed in the terminal ileum, cecum, and ascending colon with minimal staining in the rest of the colon and rectum. Eighty-three percent of adenomas expressed Le(y), with 70% showing an increased expression of Le(y) compared with normal tissue. Only 25% of metaplastic (nonneoplastic) polyps showed an increased expression of Le(y). The expression of Le(y) in adenomas was correlated with both size and degree of epithelial dysplasia of the adenomas and also showed an association with histologic type. No correlation was found with the location and morphology of the adenomas. The most strongly related parameter was the degree of dysplasia. All adenomas with severe dysplasia showed increased expression of Le(y), with 83% showing marked expression. This finding was irrespective of their size or type. Adenomas which did not exhibit severe dysplasia showed increased expression in 66% of cases, but only 18% showed marked expression. These findings show that the expression of Le(y) in colorectal lesions is associated with features related to malignant potential. Le(y) expression may provide useful prognostic information in the assessment of colorectal polyps.

Cells from two adenocarcinomas, an adenoma and a metastatic node were isolated in soft agar. Expression of antigens, CEA, Y haptenic blood group and 791T-p72, defined by a range of candidate antibodies for tumour targeting was assessed. All of the cells expressed low levels of CEA but high levels of the Y haptenic blood group antigen although there was enormous inter and intraclonal variation. Of particular interest was the membrane expression of 791T-p72 antigen on all of the dividing tumour cells as previous studies had shown that 791T/36 antibody reacted with tumour stromal elements rather than malignant cell surfaces. The DNA content was abnormal in all of the cells whether they were derived from diploid or aneuploid primary tumours. They all grew readily in athymic mice and at least one monoclonal antibody, 791T/36, localised efficiently within these xenografts. Clonogenic cells therefore expressed the three tumour-associated antigens, several at higher levels than observed in the primary tumour. Monoclonal antibody 'cocktails' should therefore allow antibody mediated drug cytotoxicity to be effective at eradicating rapidly dividing tumour cells. Images Figure 3

To assess the effectiveness of screening by faecal occult blood tests, 107,349 people without symptoms of colorectal disease identified from general practitioner records have been randomly allocated to test and control groups. 53,464 test subjects were invited to carry out the screening test; 27,651 (53%) of the 52,258 who received the tests did so. Further investigation of the 618 (2.3%) with positive tests showed 63 cancers (52% stage A) and 367 adenomas (266 subjects). Rescreening of subjects with negative results every 2 years (9510 first rescreen, 3639 second) has shown a significant fall in the rate of positive results (1.7% of 7344; 0.3% of 2906). Cancers have also been diagnosed in 20 subjects presenting in the interval between a negative test and rescreening, and in 83 non-responders. The incidence of cancer in the control group (123 subjects; 10.6% stage A) was 0.72 per 1000 person-years. Cancers detected by screening were at a less advanced pathological stage, but it is too early to show any effect of screening on mortality from colorectal cancer.

The radiolabeled monoclonal antibody 791T/36 raised against a human osteosarcoma was injected into 20 patients with known or suspected bone tumors. Gamma camera images were acquired at 48 or 72 hours after injection, and assessed for antibody localization. Positive images were obtained in all five osteosarcomas and four other primary malignant sarcomas. Two of the four other primary bone tumors gave positive images. Three patients with trauma had negative images as did one patient with Paget's disease. Two patients with suppurative disease gave positive images. The antibody localized in the majority of malignant sarcomas tested. In one tumor where tissue was available, a tumor:non-tumor ratio of 2.8:1 was measured. Repeat imaging was performed in five patients. Immunoscintigraphy using the monoclonal antibody 791T/36 has shown tumor localization in patients with bone and soft tissue sarcomas.

A total of 26,975 asymptomatic individuals were identified from family doctors' age/sex registers and randomly allocated to test or control group. The first test group (10,253) were offered 3-day fecal occult blood (FOB) testing; 3,613 (37%) completed the tests and 77 (2.1%) were found to be positive. In this group, 13 cancers were detected (3.5/1000 persons screened), of which 9 (70%) were Stage A; Of these subjects, 3349 have been rescreened at 2 years; 2799 (85%) completed the tests and 80 (2.8%) were found to be positive. Four cancers have been detected (three Stage A). In the whole test group followed for 2 years (10,462), 34 cancers have presented (17 screening detected, 3 interval cases in test responders, 14 symptomatic cancers in nonresponders), of which 14 (43%) were Stage A. In the control group (10,272 individuals), 17 patients have presented with symptomatic colorectal cancer during the 2-year follow-up, with rates of 0.9/1000 and 0.8/1000 persons/year in the first and second years of follow-up, respectively. No Stage A tumors were present. In the second test group (3,225) offered both guaiac (Hemoccult; Smith Kline Diagnostics) and immunologic (Feca EIA; Nordic) FOB tests, 1304 (44%) completed the tests, of which 126 (9.7%) were positive. Five cancers were detected (four Stage A), of which only three were positive by Hemoccult testing. In this group of test responders, one cancer has presented symptomatically at 1 year follow-up. Thus, at 2-year follow-up of the responding individuals of both cohorts of the initial screen of the test group, 5 of 21 cancers (24%) were negative by Hemoccult testing. Fecal occult blood testing has doubled the detection of colorectal cancer in the test group compared with the number presenting with symptoms in 2 years in the control group, and increased the proportion of early stage cancers (x2 = 8.0, P = < 0.001). Cancer 58:397–403, 1986.

Paget's disease of the anus is a rare disorder of controversial origin and is frequently associated with malignancy. We studied eight patients and carried out immunohistochemical studies to determine whether particular functional profiles might be indicators of a malignant association. One patient presented with synchronous carcinoma and two developed carcinomas 3 and 10 years after excision of Paget's disease. Five patients underwent wide local excision and have not developed cancer (median follow-up 6 years, range 5-13 years). However, four patients developed recurrent Paget's disease. Immunohistochemical studies showed that in general Paget cells stained positively with CAM 5·2 (a cytokeratin marker), gross cystic disease fluid protein (a marker for apocrine cells), human milk fat globule glycoprotein (HMFG 1 and 2) and carcinoembryonic antigen but negatively for PR3A5 (a marker for colonic goblet cells). Three cases had a staining profile which was quite different from that usually observed and these were associated with malignancy. One showed an antigenic profile more typical of a large bowel carcinoma. Paget's disease of the anus appears to run one of two clinical courses: to develop malignancy; or to recur locally, often on repeated occasions. Wide local excision is the treatment of choice but long-term follow-up is necessary because of the cancer risk. An immunohistochemical staining pattern which is different from usual may indicate a higher malignant risk and/or identify some cases of Paget's disease as representing a downward ‘pagetoid’ extension from a anorectal adenocarcinoma rather than a true epidermotropic apocrine neoplasm of the perianal skin.

Fifty-six patients with gastrointestinal cancers and four patients with benign colorectal tumours have been injected with radiolabelled anti-tumour monoclonal antibody (791T/36) to assess the degree of localization of the antibody by external scintiscanning and measurements on resected specimens. Twenty-nine patients with primary colorectal cancer showed increased uptake of the radiolabelled antibody in the resected tumours, with a tumour to normal tissue (T:NT) ratio of 2·5:1. All but two of fifteen patients with recurrent or metastatic tumour showed positive images of the deposits on external scintiscanning. Twelve patients with noncolonic gastrointestinal malignancy were studied and in only two patients were tumours demonstrated by external scanning. There were no positive images in four patients with benign colonic disease nor could increased uptake of radiolabelled antibody be demonstrated in the resected specimens. Immunohistology and autoradiography have shown that the antibody can be demonstrated in the pseudoacini and stroma of colon cancer. There are indications that this may represent localization to a cell surface antigen which becomes detached in the processing of the histological sections. It seems that in the gastrointestinal tract the monoclonal antibody 791T/36 is consistently taken up by colorectal cancer. Only a few noncolonic cancers and no benign colonic tumours take up the antibody. This antibody uptake may prove of value in the detection of occult metastases and in the targeting of antitumour agents.

A major problem in the chemotherapy of colorectal cancers is their resistance to most cytotoxic drugs which may be due to insufficient cellular transport. Drugs conjugated to monoclonal antibodies recognising tumour antigens may overcome these difficulties by providing access of active agents to the tumour cells. The anti-tumour monoclonal antibody shown to localise in patients with colorectal cancer, 791T/36, has been investigated as a potential targeting antibody. Eight cell lines were established from surgically resected material and were shown to bind 791T/36 antibody. They were screened for their sensitivity to methotrexate, 5-fluorouracil and daunomycin. Although 5-fluorouracil is the drug of choice for chemotherapy of colorectal cancer it was the most cytotoxic drug in only 2 of the 8 cell lines. Only the 4 cell lines which were resistant to methotrexate showed less cytotoxicity with methotrexate than 5-fluorouracil. The cell lines which were resistant to methotrexate were more sensitive to 791T/36-methotrexate conjugates. Daunomycin was the most cytotoxic drug in 4 of the 8 cell lines. However, a similar cytotoxicity was observed for free drug and 791T/36 daunomycin in the two lines tested. Selective monoclonal antibody drug conjugates may offer a solution to treatment of tumours which are resistant to classical chemotherapeutic agents. This is the first report to show that newly established cell lines that are resistant to classical chemotherapeutic agents are rendered sensitive when the drug enters the cell as a drug monoclonal antibody carrier.