PROSPER: a randomised comparison of surgical treatments for rectal prolapse.

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.

Fibrin glue for the treatment of fistulae in ano--a method worth sticking to?

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.

Complex perirectal sepsis: clinical classification and imaging.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Future studies should determine both what sequential imaging algorithms for imaging are cost-effective as well as predictive of fistula cure.

Enhanced expression of the complement regulatory protein CD55 predicts a poor prognosis in colorectal cancer patients.

This study prospectively correlated the level of expression of CD55 on tumours with 7-year survival in 136 colorectal cancer patients. Patients with tumours expressing high levels of CD55 had a significantly worse survival (24%) than patients with low CD55 levels (50%, p<0.02). A similar difference was seen for patients (Duke's B or C) with a high risk of recurrence (29% vs 58%, p<0.05). Furthermore, there was a progressive deterioration in prognosis with increasing antigen expression ( p=0.01). It remains unclear if CD55 is overexpressed by tumours to protect them from complement or if it is related to the recent observation that CD55 is a ligand for the T-cell activation antigen CD97. However, it is a marker of aggression, as colorectal cancer patients whose tumours overexpress CD55 have a significantly reduced 7-year survival.

V-Y advancement flap for treatment of fistula-in-ano.

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.

Defunctioning loop ileostomy and stapled side-to-side closure has low morbidity.

INTRODUCTION: Low pelvic anastomoses are associated with a high leak rate. Therefore, defunctioning loop ileostomies are being increasingly fashioned to protect against the consequences of a leak. However, the reported complication rates of such stoma creation and closure is between 5.7-69%. AIMS: To determine the outcome associated with construction and side-to-side closure of loop ileostomies in one specialist unit. PATIENTS AND METHODS: Data were obtained from a computer audit and case note analysis. RESULTS: Between 1994 and 1998, 71 patients (41 M, 30 F) with a median age of 51 years (range 19-88 years) had a loop ileostomy constructed for: (i) 26 ileoanal pouches; (ii) 36 left colonic and rectal resections; and (iii) 9 for other reasons. Side-to-side stoma closure was achieved using a GIA linear stapler through a parastomal incision. The median hospital stay following stoma creation was 12 days (range 7-63 days) and stoma closure was 7 days (range 6-16 days). The median time to closure was 140 days (range 10-790 days). There were no ileostomy-related deaths. There were 10 (13.8%) ileostomy-related complications, 4 following creation and 6 following closure. CONCLUSIONS: Loop ileostomy is easy to create and close and is associated with a low morbidity. Therefore, we recommend a defunctioning ileostomy as a procedure of choice for temporary faecal diversion for complex colorectal surgery.

Lateral repair of parastomal hernia.

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.

Risks, costs, and compliance limit colorectal adenoma surveillance: lessons from a randomised trial.

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.

The risks of screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer.

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.

Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.

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.

Endoscopic screening of relatives of patients with colorectal cancer.

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.

Chemical and immunological testing for faecal occult blood in screening subjects at risk of familial colorectal cancer.

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.

Magnetic resonance imaging in the management of fistula in ano.

Fistula-in-ano is a common condition in which accurate diagnosis of the fistula track is essential as inadequate assessment and surgical treatment may lead to multiple unnecessary operations and may also render the patient incontinent. Several studies have suggested that Magnetic Resonance Imaging (MRI) can accurately identify the fistula track in relation to the sphincter complex. The aim of this study was to investigate the value of the routine use of completely non-invasive pre-operative MRI in patients with suspected fistula-in-ano. Each scan was reported by a consultant radiologist on two occasions to determine whether the radiologist's opinion had changed and/or become more accurate with further experience. Surgical assessment of the fistula was performed under general anaesthesia by one surgeon without knowledge of the result of the MRI scan. The results of the surgical assessment and the MRI scan were compared and the surgical procedure completed. Thirty three patients with a clinical diagnosis of fistula-in-ano were treated and 27 subsequently confirmed to have a fistula. MRI detected 42% of tracks, identified correctly on initial assessment which increased to 50% at the end of the study, 63% and 74% of internal openings, 33% and 46% of external openings and 50% and 33% of abscesses. These data suggest that there is a learning curve for radiologists undertaking MRI scanning for fistula in ano, this is probably because the pathology of fistula in ano and anatomy of the anal sphincter complex are relatively new to radiologists. Routine MRI scanning of patients with fistula-in-ano is not necessary but there may be a role for MRI in assessing complex or difficult fistulae.

Use of glyceryl trinitrate ointment in the treatment of anal fissure.

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 < 0.001). Healing was complete in 11 patients at 4 weeks and in 18 at 6 weeks. The fissure recurred in four patients after cessation of treatment; three were successfully treated by further glyceryl trinitrate. Mild headache occurred in four patients. Anal fissure can be successfully treated with 0.2 per cent glyceryl trinitrate ointment applied topically.

Locally advanced breast cancer: long-term results of a randomized trial comparing primary treatment with tamoxifen or radiotherapy in post-menopausal women.

We have previously reported the early results of a randomized cross-over study of radical radiotherapy vs tamoxifen in patients with locally advanced breast cancer. This study has now recruited 143 patients with a median time from randomization of almost 10 years for both groups. Seventy-three patients received 20 mg tamoxifen twice daily, and 70 had primary radiotherapy at a dose of 40 Gy, which is a lower dose than currently administered. The treatment groups were similar in age, size of tumour and oestrogen receptor status. There was no significant difference between the two treatment groups for the combined initial response and static disease rates (89% for radiotherapy and 78% for tamoxifen, P = 0.15). The median duration of initial response was 12 months for both groups. When patients crossed over to the alternative therapy on local relapse, there was no difference in response/static disease rates (P = 0.34) and duration of response (P = 0.76). A non-significant prolongation of the metastatic-free interval in favour of tamoxifen (P = 0.08) was identified, although there was no difference in survival outcome (P = 0.38). This study shows that in this group of patients primary tamoxifen offers a similar clinical benefit to primary radiotherapy at a dose of 40 Gy, and is therefore an acceptable alternative primary treatment.

Transanal endoscopic microsurgery--initial experience from three centres in the United Kingdom.

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.

Five-year prospective study of DNA tumor ploidy and colorectal cancer survival.

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.