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Aim A questionnaire completed by members of the ACPGBI in 1997 was a precursor to the PROSPER trial. It showed a significant variation in favoured practice for the surgical treatment of external rectal prolapse. We repeated the same questionnaire to assess how practice has changed since the completion of the trial and its publication. Method An online survey was circulated to all members of the ACPGBI with identical questions to those used in the original in 1997. Results Similar numbers of recipients responded (122/791 [15.4%] in 2014;153/600 [25.5%] in 1997). The median number of operations per surgeon per year was unchanged (6 [0-30] vs 6 [0–25]). The percentage of surgeons who favoured an abdominal approach in fit patients in 1997 rose significantly from 63.5% to 81.7% in 2014 (P

Background: The first UKCCCR Anal Cancer Trial (1996) demonstrated the benefit of chemoradiation over radiotherapy (RT) alone for treating epidermoid anal cancer, and it became the standard treatment. Patients in this trial have now been followed up for a median of 13 years. Methods: A total of 577 patients were randomised to receive RT alone or combined modality therapy using 5-fluorouracil and mitomycin C. All patients were scheduled to receive 45 Gy by external beam irradiation. Patients who responded to treatment were recommended to have boost RT, with either an iridium implant or external beam irradiation. Data on relapse and deaths were obtained until October 2007. Results: Twelve years after treatment, for every 100 patients treated with chemoradiation, there are an expected 25.3 fewer patients with locoregional relapse (95% confidence interval (CI): 17.5–32.0 fewer) and 12.5 fewer anal cancer deaths (95% CI: 4.3–19.7 fewer), compared with 100 patients given RT alone. There was a 9.1% increase in non-anal cancer deaths in the first 5 years of chemoradiation (95% CI +3.6 to +14.6), which disappeared by 10 years. Conclusions: The clear benefit of chemoradiation outweighs an early excess risk of non-anal cancer deaths, and can still be seen 12 years after treatment. Only 11 patients suffered a locoregional relapse as a first event after 5 years, which may influence the choice of end points in future studies.

Purpose: This study set out to determine the impact of a positive circumferential resection margin (CRM) (R1-R2) and pathologic downstaging on local recurrence and survival in patients with borderline resectable or unresectable rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy (CRT). Methods and Materials: A total of 150 patients with locally advanced rectal cancer were treated with long-course neoadjuvant CRT using low-dose folinic acid and 5-fluorouracil. CRT was followed 6–12 weeks later by surgical excision. The CRM rate and incidence, site, and pattern of local and systemic recurrences were recorded. The median follow-up was 25 months. Results: The overall median survival was 37 months, with a 5-year overall survival rate of 34%. Of the 150 patients, 122 underwent curative resection; 12% had a complete pathologic response, and downstaging to pT1-T2 occurred in an additional 16%. A negative CRM (R0) was achieved in 65% overall (98 of 150). Local recurrence occurred in 10% of those with R0 resection and 62% of those with R1-R2 resections. Distant metastases occurred in 29% of those with R0 resections and 75% of those with R1-R2 resections. The 3-year disease-free and 3-year overall survival rate was 9% and 25% and 52% and 64%, respectively, for patients with and without a histologically positive CRM. Conclusion: After 5-fluorouracil–based CRT, a positive CRM predicted for a high risk of subsequent local recurrence and a 3-year disease-free survival rate of only 9%. For this reason, the CRM should be considered a major prognostic factor and should be validated in future trials as an early alternative clinical endpoint.

Summary Background The effectiveness of surgery for colorectal cancer depends on it being carried out safely, which allows most patients to return to productive lives, with an improved postoperative life expectancy, or at least one that is not diminished by the surgery. Because colorectal cancer is a major cause of morbidity and mortality in elderly people, we have examined how the outcomes of surgery in elderly patients differ from those in younger patients. Methods We did a systematic review of published and aggregate data provided by investigators. Studies were identified by computerised and manual searches of published and unpublished reports, scanning references, and contacting investigators. Within each study, outcomes for patients aged 65–74 years, 75–84 years, and 85+ years were expressed in relation to those aged less than 65 years. Findings From 28 independent studies, and a total of 34194 patients, we found that elderly patients had an increased frequency of comorbid conditions, were more likely to present with later-stage disease and undergo emergency surgery, and less likely to have curative surgery than younger patients. The incidence of postoperative morbidity and mortality increased progressively with advancing age. Overall survival was reduced in elderly patients, but for cancer specific survival age-related differences were much less striking. Interpretation The relation between age and outcomes from colorectal cancer surgery is complex and may be confounded by differences in stage at presentation, tumour site, pre-existing comorbidities, and type of treatment received. However, selected elderly patients benefit from surgery since a large proportion survive for 2 or more years, irrespective of their age.

PURPOSE: This study was designed to evaluate the operative treatments performed on patients with perianal Crohn's disease at a tertiary referral colorectal university hospital and to determine the efficacy of management by assessing patient satisfaction. METHODS: A retrospective survey included 59 patients with perianal Crohn's disease who had undergone surgery during the period of 1991 to 1993, inclusive. RESULTS: Twenty-seven patients were treated by laying the fistula open (81 percent successful), and another 27 cases were treated with a loose seton (85 percent successful). Five cases were complicated fistulas and underwent diversionary stomas as part of a primary procedure. Overall success rate, as judged by patient satisfaction, was 83 percent. CONCLUSION: Conservative surgery has a role in management of perianal Crohn's disease. Patient satisfaction can be achieved without complete healing. Better preoperative assessment may improve results further.

Purpose: The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. Methods and Materials: A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone or CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Results: Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35–1.12; p = 0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48–1.68; p = 0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p = 0.51). OTT was longer by 6.1 days for EBRT (p = 0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p = 0.03). Conclusions: These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control.

Summary Background Colorectal cancer is the third most common cancer worldwide and has a high mortality rate. We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 years of age can substantially reduce colorectal cancer incidence and mortality. Methods This randomised controlled trial was undertaken in 14 UK centres. 170 432 eligible men and women, who had indicated on a previous questionnaire that they would accept an invitation for screening, were randomly allocated to the intervention group (offered flexible sigmoidoscopy screening) or the control group (not contacted). Randomisation by sequential number generation was done centrally in blocks of 12, with stratification by trial centre, general practice, and household type. The primary outcomes were the incidence of colorectal cancer, including prevalent cases detected at screening, and mortality from colorectal cancer. Analyses were intention to treat and per protocol. The trial is registered, number ISRCTN28352761. Findings 113 195 people were assigned to the control group and 57 237 to the intervention group, of whom 112 939 and 57 099, respectively, were included in the final analyses. 40 674 (71%) people underwent flexible sigmoidoscopy. During screening and median follow-up of 11·2 years (IQR 10·7–11·9), 2524 participants were diagnosed with colorectal cancer (1818 in control group vs 706 in intervention group) and 20 543 died (13 768 vs 6775; 727 certified from colorectal cancer [538 vs 189]). In intention-to-treat analyses, colorectal cancer incidence in the intervention group was reduced by 23% (hazard ratio 0·77, 95% CI 0·70–0·84) and mortality by 31% (0·69, 0·59–0·82). In per-protocol analyses, adjusting for self-selection bias in the intervention group, incidence of colorectal cancer in people attending screening was reduced by 33% (0·67, 0·60–0·76) and mortality by 43% (0·57, 0·45–0·72). Incidence of distal colorectal cancer (rectum and sigmoid colon) was reduced by 50% (0·50, 0·42–0·59; secondary outcome). The numbers needed to be screened to prevent one colorectal cancer diagnosis or death, by the end of the study period, were 191 (95% CI 145–277) and 489 (343–852), respectively. Interpretation Flexible sigmoidoscopy is a safe and practical test and, when offered only once between ages 55 and 64 years, confers a substantial and longlasting benefit. Funding Medical Research Council, National Health Service R&D, Cancer Research UK, KeyMed.

Objectives Comorbid conditions in colorectal cancer patients can influence both clinical eligibility for treatment and survival. We aimed to evaluate the effect of comorbidity on 1 year survival from colorectal cancer, and to assess whether this effect varied with the timing of the comorbidity in relation to the cancer diagnosis. Study design and setting A population based cohort of 29 563 colorectal cancer patients diagnosed between 1997 and 2004 in the North West of England was evaluated. The excess hazard of death up to 1 year after diagnosis was estimated using deprivation and region specific life tables to adjust for background mortality. Results were adjusted for age and stage at diagnosis. Results Comorbid conditions diagnosed during the period 18 to 6 months before the diagnosis of colorectal cancer were strongly associated with lower survival at 1 year. Stage and age remained the strongest predictors of cancer related mortality even after adjustment for comorbidity. Conclusions Administrative data provide a good estimate of the prevalence of most comorbid conditions but may be biased for some comorbid conditions that can be contra-indicators for cancer treatment. The time window in which a comorbid condition occurs in relation to the cancer diagnosis should be taken into account. Adjustment should be carried out, where possible, to provide more robust and clinically appropriate comparisons of population based cancer patient survival.

The hypoxia-mediated response of tumours is a major determining factor in growth and metastasis. Understanding tumour biology under hypoxic conditions is crucial for the development of antiangiogenic therapy. Using one of the largest cohorts of rectal adenocarcinomas to date, this study investigated hypoxia-inducible factor-1alpha (HIF-1alpha) and HIF-2alpha protein expression in relation to rectal cancer recurrence and cancer-specific survival. Patients (n=90) who had undergone surgery for rectal adenocarcinoma, with no prior neoadjuvant therapy or metastatic disease, and for whom adequate follow-up data were available were selected. Microvessel density (MVD), HIF-1alpha and HIF-2alpha expressions were assessed immunohistologically with the CD34 antibody for vessel identification and the NB100-131B and NB100-132D3 antibodies for HIF-1alpha and HIF-2alpha, respectively. In a multifactorial analysis, results were correlated with tumour stage, recurrence rate and long-term survival. Microvessel density was higher across T and N stages (P50% of rectal cancers (HIF-1alpha, 54%, 48/90; HIF-2alpha, 64%, 58/90). HIF-1alpha positivity was associated with both TNM stage (P

A newly identified myopathy of the internal anal sphincter is described. In the affected family, at least one member from each of five generations had severe proctalgia fugax; onset was usually in the third to fifth decades of life. Three members of the family have been studied in detail. Each had severe pain intermittently during the day and hourly during the night. Constipation was an associated symptom, in particular difficulty with rectal evacuation. Clinically the internal anal sphincter was thickened and of decreased compliance. The maximum anal canal pressure was usually increased with marked ultraslow wave activity. Anal endosonography confirmed a grossly thickened internal anal sphincter. Two patients were treated by internal anal sphincter strip myectomy; one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain. The hypertrophied muscle in two of the patients showed unique myopathic changes, consisting of vacuolar changes with periodic acid-Schiff-positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis. In vitro organ-bath studies showed insensitivity of the muscle to noradrenaline, isoprenaline, carbachol, dimethylpiperazinium, and electrical-field stimulation. Immunohistochemical studies for substance P, calcitonin gene-related peptide, galanin, neuropeptide Y, and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue. A specific autosomal-dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized.

Background Despite the increasing use of palliative chemotherapy for advanced colorectal cancer, there remains uncertainty as to the true effectiveness of this intervention. This review was therefore undertaken to assess the available evidence for the benefit of palliative chemotherapy in this disease. Objectives To determine the benefits and harms of palliative chemotherapy in patients with locally advanced or metastatic colorectal cancer. A secondary objective was to investigate outcomes for younger and elderly patients. Search methods Trials were identified by computerised and hand searches of the literature, scanning references and contacting investigators. Selection criteria All randomised controlled trials of palliative chemotherapy compared with supportive care alone in patients with advanced or metastatic colorectal cancer. Both randomised and non-randomised studies were considered when searching for data on quality of life, resource use and cost effectiveness of palliative chemotherapy. Data collection and analysis Investigators from all eligible studies were asked to supply individual patient data. Meta-analysis was performed using both published data and individual patient data. Studies were grouped according to whether chemotherapy was administered regionally or systemically. Main results 13 randomised controlled trials representing a total of 1365 randomised patients met the inclusion criteria. Meta-analysis of a subset of trials that provided individual patient data demonstrated that palliative chemotherapy was associated with a 35% (95% CI 24% to 44%) reduction in the risk of death. This translates into an absolute improvement in survival of 16% at both 6 months and 12 months and an improvement in median survival of 3.7 months. The overall quality of evidence relating to treatment toxicity, symptom control and quality of life was poor. Authors' conclusions Chemotherapy is effective in prolonging time to disease progression and survival in patients with advanced colorectal cancer. The survival benefit may be underestimated by this meta-analysis, as a proportion of patients in the control arms of some trials received chemotherapy. No age related differences were found in the effectiveness of chemotherapy, but elderly patients were under represented in trials. Treatment toxicity and impact upon quality of life and symptom control have been inadequately assessed in the majority of trials and further research is needed to clarify the palliative benefit of chemotherapy.

3500 Background: Intensive long-term follow-up after surgery for colorectal cancer is common practice but neither the actual benefit nor the optimal methodology is known. Methods: Pragmatic factorial randomised controlled trial in 39 UK hospitals, comparing minimum follow-up (which included a single CT scan at 12-18 months) with 3-6 monthly blood carcinoembryonic antigen (CEA) testing and 6-12 monthly computerised tomography (CT) imaging of the chest, abdomen and pelvis following 1202 participants for 3-5 (mean 3.7) years. Results: The proportion of participants with recurrence treated surgically with curative intent was lower than predicted (6.0% overall) but was about 3x higher in the more intensive than minimum follow-up arms (p=0.019). The adjusted odds were 2.7 for CEA only (p=0.035) and 3.4 for CT only (p=0.007); the absolute differences in detection rate in the more intensive arms compared to minimum follow-up were 4.3-5.7% (5.8-8.0% per protocol). Combining CEA and CT provided no additional benefit (adjusted odds for CT+CEA arm = 2.9). The absolute difference in the proportion of participants with recurrence treated surgically with curative intent in the factorial comparison was 1.4% for CEA (p=0.28) and 2.8% for CT (p=0.04). There was no statistical difference in colorectal cancer deaths nor overall deaths in the minimum compared to the intensive follow-up arms. Conclusions: Both regular CEA measurement and CT scanning result in significantly higher rates of diagnosis of operable recurrent colorectal cancer compared to minimal follow up. There is no benefit in monitoring with both CEA and CT. To date no difference in the overall mortality has been demonstrated. CEA monitoring combined with a single CT scan at 12-18 months seems likely to be cost effective. Clinical trial information: 41458548.

We have used an avidin-biotin immunoperoxidase technique to localise epithelial cadherin (E-cadherin), a calcium-dependent cell-cell adhesion molecule, in 107 paraffin-embedded sections from 93 patients consisting of 24 with colorectal adenoma, 55 with rectal carcinoma and 14 with liver metastases. The corresponding primary colorectal tumours were also studied in these cases. E-cadherin was expressed by normal colorectal epithelial cells with typical membranous staining at the intercellular junctions. Loss of normal membranous E-cadherin expression and presence of cytoplasmic staining were found frequently in adenomas larger than 1 cm (P

Moderator: Dr. Jass. The staging of colorectal cancer, a seemingly innocuous and dry subject, has within the last few years become topical and indeed spiked with emotion. A panel of five surgeons and five histopathologists, all with a special interest in colorectal cancer, have been invited to respond to a series of pertinent but fairly open-ended questions. I hope that you will find their answers both thought-provoking and instructive.

Anal fistula has long been notorious for its tendency to recur after operation and for the great difficulty in achieving a lasting cure while avoiding damage to the mechanism of anal continence. It was these unfavourable circumstances that led some surgeons to take a special interest in its management and were responsible for the establishment by Frederick Salmon in London 152 years ago of St. Mark’s Hospital, which at its inception appropriately bore the name “St. Mark’s Hospital for Fistula and other Diseases of the Rectum”. Anal fistula could thus be regarded as having played a key role in the creation of proctology as a special surgical discipline.

The moderator and participants in this symposium are some of the members of the Leeds Castle Polyposis Group, set up in 1985 to promote cooperative investigation and prospective research in this field. Initial studies have summated data on the group’s screening and surgical practices and their experiences with desmoid disease and upper gastrointestinal neoplasia. The group plans to publish these joint studies in the future; in the meantime we congratulate the participants and moderator in our Symposium for this unique contribution to the literature on this difficult subject.