Aim There is a requirement for an expansive and up to date review of the management of emergency colorectal conditions seen in adults. The primary objective is to provide detailed evidence-based guidelines for the target audience of general and colorectal surgeons who are responsible for an adult population and who practise in Great Britain and Ireland. Methods Surgeons who are elected members of the Association of Coloproctology of Great Britain and Ireland Emergency Surgery Subcommittee were invited to contribute various sections to the guidelines. They were directed to produce a pathology-based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. Each author was asked to provide a set of recommendations which were evidence-based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after two votes were included in the guidelines. Results All aspects of care (excluding abdominal trauma) for emergency colorectal conditions have been included along with 122 recommendations for management. Conclusion These guidelines provide an up to date and evidence-based summary of the current surgical knowledge in the management of emergency colorectal conditions and should serve as practical text for clinicians managing colorectal conditions in the emergency setting.

Colorectal DiseaseVolume 22, Issue 4 p. 364-372 For DebateOpen Access The use of oral antibiotics and mechanical bowel preparation in elective colorectal resection for the reduction of surgical site infection S. E. Duff, Corresponding Author S. E. Duff sarah.duff@mft.nhs.uk @SarahDuff3 orcid.org/0000-0001-6760-6451 Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UKSearch for more papers by this authorC. L. F. Battersby, C. L. F. Battersby Wrexham Maelor Hospital, Wrexham, UKSearch for more papers by this authorR. J. Davies, R. J. Davies Cambridge Colorectal Unit, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, UKSearch for more papers by this authorL. Hancock, L. Hancock Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UKSearch for more papers by this authorJ. Pipe, J. Pipe Patient Liaison Group ACPGBI, Sheffield, UKSearch for more papers by this authorS. Buczacki, S. Buczacki Cambridge Colorectal Unit, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, UKSearch for more papers by this authorJ. Kinross, J. Kinross Department of Surgery and Cancer, St Mary's Hospital, Imperial College, London, UKSearch for more papers by this authorA. G. Acheson, A. G. Acheson Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, National Institute for Health Research (NIHR), Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, University of Nottingham, Nottingham, UKSearch for more papers by this authorC. J. Walsh, C. J. Walsh Wirral University Teaching Hospitals NHS Foundation Trust, Wirral, UKSearch for more papers by this authoron behalf of the Association of Coloproctology of Great Britain and Ireland S. E. Duff, Corresponding Author S. E. Duff sarah.duff@mft.nhs.uk @SarahDuff3 orcid.org/0000-0001-6760-6451 Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UKSearch for more papers by this authorC. L. F. Battersby, C. L. F. Battersby Wrexham Maelor Hospital, Wrexham, UKSearch for more papers by this authorR. J. Davies, R. J. Davies Cambridge Colorectal Unit, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, UKSearch for more papers by this authorL. Hancock, L. Hancock Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UKSearch for more papers by this authorJ. Pipe, J. Pipe Patient Liaison Group ACPGBI, Sheffield, UKSearch for more papers by this authorS. Buczacki, S. Buczacki Cambridge Colorectal Unit, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, UKSearch for more papers by this authorJ. Kinross, J. Kinross Department of Surgery and Cancer, St Mary's Hospital, Imperial College, London, UKSearch for more papers by this authorA. G. Acheson, A. G. Acheson Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, National Institute for Health Research (NIHR), Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, University of Nottingham, Nottingham, UKSearch for more papers by this authorC. J. Walsh, C. J. Walsh Wirral University Teaching Hospitals NHS Foundation Trust, Wirral, UKSearch for more papers by this authoron behalf of the Association of Coloproctology of Great Britain and Ireland First published: 14 February 2020 https://doi.org/10.1111/codi.14982Citations: 4AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Introduction Surgical site infection (SSI) is a major cause of morbidity worldwide following elective colorectal resection, affecting up to 20% of patients 1-3. Reduction in SSI rates requires a multi-faceted approach 4 and can be achieved with the use of SSI reduction bundles 5. Such bundles include prophylactic intravenous antibiotics 6 which represent an undisputed standard of care 4. They do not include the use of mechanical bowel preparation (MBP) alone which is not recommended in elective colonic resection to reduce SSI 7-9, although may offer an advantage in elective rectal resection 10. A long-standing area of controversy is the use of mechanical bowel preparation and oral antibiotics (MOAB) prior to elective colorectal resection 11, 12. Marked differences exist between clinicians worldwide 13. Recent guidelines from the American Society of Colon and Rectal Surgeons strongly recommend the use of MOAB in elective colorectal resection to reduce SSI 14, 15. Other international bodies have recognized the increasing body of evidence and altered their recommendations in a more conservative manner but stopped short of endorsing this practice because of the lack of Level 1 evidence 16. This paper summarizes the arguments for and against the use of MOAB in elective colorectal resection, highlighting the areas of controversy and evidence gaps, and provides pragmatic suggestions for colorectal practice (Fig. 1). Figure 1Open in figure viewerPowerPoint Arguments for and against the use of mechanical bowel preparation and oral antibiotics in elective colorectal resection. MOAB, mechanical bowel preparation and oral antibiotics; MIS, minimally invasive surgery; ERAS, enhanced recovery after surgery; BMI, body mass index; SSI, surgical site infection; ABx, antibiotics; CDI, Clostridium difficile infection; QI, quality improvement. Arguments supporting the use of MOAB The combination of MOAB in elective colorectal resection is associated with lower rates of SSI. Numerous reports from the North American Surgical Quality Improvement Program (NSQIP) show improved clinical outcomes after varying versions of preoperative MOAB 17-31. These observational studies include many thousands of patients undergoing elective surgery and show that the combination of MOAB in comparison to MBP alone is associated with a reduction in SSI of about 50%. Similar reductions are seen in numerous randomized controlled trials (RCTs) 32-37, observational studies 13 and meta-analyses, both in meta-analyses of RCTs alone 2, 38-40 and in those analysing both RCTs and observational studies 41, 42. There seem to be additional patient benefits in using MOAB. Over the last decade, accumulating reports have highlighted reductions in anastomotic leak (AL), ileus, readmission rates, reoperation rates and even mortality. However, these findings are not consistent across all studies. Positive effects of MOAB have been seen in multiple retrospective studies 13, 18, 19, 21-31, 43. The beneficial effects may be more evident in left-sided colonic resections or rectal resections 22, 29, 44. Several underpowered RCTs, however, have shown no difference in AL rates 36, 45. Meta-analyses vary in their conclusions regarding the additional benefits of MOAB. No differences in AL rates were seen in a meta-analysis including 16 RCTs published between 1979 and 2007 38 nor in a recent network meta-analysis including 8458 patients in 38 RCTs, whereas significant multiple additional benefits were reported in two recent large meta-analyses, although these effects were less evident when oral antibiotics (OAB) were considered alone 41, 42. Developing evidence implicating intraluminal bacteria in the pathogenesis of AL and reduction in AL with locally administered antibiotics and selective gut decontamination regimes 46 may go part way to explaining the reduction in AL seen with MOAB. The consequences of infectious complications, such as SSI and AL, may persist for years and are associated with a reduction in quality of life years after the initial surgery 47. There is extensive evidence to show that SSI is a risk factor for the development of incisional hernia 48-50 which is a common, complex and costly complication of colorectal surgery associated with considerable morbidity. Septic complications increase the permanent stoma rate and in rectal resections supposedly temporary diverting ileostomies are not reversed in more than a third of cases 51, almost always due to a septic anastomotic complication. There is also evidence to support increased risk of local and distant cancer recurrence and reduced survival following AL 52-56. Reducing these complications by using MOAB is therefore a very attractive proposition yet possible widespread reintroduction of this policy has raised concerns that the incidence of Clostridium difficile related infections (CDI) may rise. A large body of evidence refutes this concern. Only two published studies show an increase in CDI rates 57 or readmissions due to CDI 18, whereas two retrospective studies show a beneficial effect. Kim et al. 19 showed that patients having MOAB had a lower CDI rate than those with no bowel preparation (0.5% vs 1.8%, P = 0.01) while Al-Mazrou et al. 58 showed a similar reduction with OAB alone. The majority of studies show no differences in CDI rates in patients exposed to OAB. This holds true for retrospective studies 30, 31, 59-61, RCTs 33-37, 45 and in meta-analysis 42. There is no evidence of harm in terms of increase in CDI rates by using MOAB. Arguments against the use of MOAB There is still a lack of high quality supporting Level 1 evidence, coupled with concerns around antimicrobial stewardship, choice of antibiotics, negative patient experience and the unknown, little understood, short-, medium- and long-term consequences on the microbiome and what this may mean for other oncological outcomes. The majority of the evidence showing benefit from MOAB is from big datasets, such as NSQIP and the European Society of Coloproctology (ESCP) snapshot audit 62. The North American registry data have influenced the American guidelines strongly where it is summarized as Level 1b (strong recommendation; moderate quality evidence) 15. This recommendation arises from the inclusion of ‘exceptionally strong evidence from observational studies’. However, these data have been criticized 11 for use of multiple retrospective reports using the same overlapping datasets and heterogeneity between groups. In many reports, the groups that receive MOAB tend to be younger, fitter, with fewer comorbidities, lower corticosteroid use and earlier stage disease which may contribute to their lower SSI rates. Despite the large numbers in these datasets, this evidence may not be robust. Irrespective of data quality, arguments against the routine introduction of MOAB prior to elective bowel resection centre around the fact that SSI reduction bundles alone can achieve low rates of SSI without necessarily including MOAB. In addition, it is also questioned whether OAB alone are enough to reduce SSI. In a similar vein, any potential reduction in AL rates achieved by implementation of safer anastomosis bundles (ongoing ESCP EAGLE study) or adoption of new technology (ongoing IntAct study) may make possible reductions in AL through use of MOAB less relevant. Evidence based care bundles focused on reducing SSI rates have been successfully implemented in many institutions over the last 10 years. In the UK, SSI bundles have been created based on guidelines from the National Institute for Health and Care Excellence, the World Health Organization and Health Protection Scotland with additional components added from the published literature 4, 63, 64. In the USA, similar national guidelines have been formulated by the American College of Surgeons and the Centers for Disease Control and Prevention 65, 66. Application of SSI care bundles form a recommended component of enhanced recovery guidelines 14. The content of SSI care bundles varies but will contain common and variable components. Common shared components include prophylactic intravenous antibiotics, preoperative bathing, hair removal and maintenance of normoglycaemia and normothermia. Less uniformly used interventions include smoking cessation, MRSA screening, 2% alcoholic chlorhexidine skin preparation, wound protectors, antibiotic impregnated sutures, change of gloves and instruments prior to skin closure, novel wound closure devices and MOAB. Compliance to care bundles can be challenging and resource intensive 67 and requires continual audit and real-time feedback to alter practice 68. Financial incentives and penalties in North America surrounding potentially preventable SSIs have resulted in significant reductions in SSI in major institutions showing that this can be achieved in practice and sustained over time 69, 70. Implementation of SSI care bundles has been shown to reduce SSI rates by up to 40% 68, 69, 71-74. The majority of the published studies are cohort studies. However, two RCTs have been carried out 75, 76. Despite clear heterogeneity between these studies two meta-analyses have also demonstrated the effectiveness of SSI care bundles 5, 77. The results clearly show that SSI bundles are effective in reducing SSI rates irrespective of whether MOAB form part of the bundle. Individual institutions can achieve rates of SSI with implementation of SSI reduction bundles as low as 1.8% 78. However, arguably it is more important to define which of the components of SSI bundles contribute the most to the effectiveness of the intervention. A recent meta-analysis 77 attempted to address this through sub-group analysis and identified MOAB, a separate sterile instrument closure tray and glove change prior to closure as providing ‘significantly greater SSI risk reduction’. Interestingly, the one study in this meta-analysis that failed to show effectiveness of bundle implementation was a well-designed RCT which omitted MOAB from the experimental arm of the trial. These studies also suffer from differences in compliance levels and how SSI rates were calculated as well as publication bias. Cumulatively, SSI bundles are evidently effective and should be standard of care 79. It has been assumed that MBP is a requirement in order for OAB to be effective. The administration of MBP prior to elective colectomy is considered unpleasant by many patients, but few studies have taken patient satisfaction into consideration. Taking bowel preparation, often for the second time in a few weeks, may add considerably to the anxiety and distress experienced by the patient before major elective colorectal surgery. The available bowel cleansing agents are often poorly tolerated, time consuming and have unpleasant side-effect profiles, resulting in reduced compliance and poor bowel preparation 80. Preparations containing polyethylene glycols are diluted in large volumes of water (up to 4 l) and have an unpalatable taste 81. Elderly patients, in particular, find it hard to drink the large volumes of fluid required 82. Sodium phosphate preparations are better tolerated due to the smaller volume of liquid (300 ml water) and palatability 83 but are associated with safety concerns such as major fluid and electrolyte shifts and so should be avoided in patients with chronic kidney disease, congestive cardiac failure, cirrhosis or in patients with electrolyte disturbances 81. Difficulties in administering MBP may also be anticipated in other patient groups including patients with poor reading skills, immobility or frailty or patients taking multiple medications. Patient concerns about taking MBP underline the need to question whether SSI reduction may be brought about by OAB alone. The need for an RCT to determine this has long been discussed 17, 84, 85, because data on OAB alone are contradictory. Different reports show that the use of OAB alone is worse than 24, 25, 27, 29-31, 43, 86, equivalent to 22, 26, 28, 42, 87 or better than 17, 20, 32 the MOAB combination in reduction of SSI. The problems are a lack of RCTs that focus on OAB alone in the absence of MBP, small numbers in the OAB alone groups and selection bias in the cohort studies. In the largest and most recent meta-analysis 42, SSI rates were compared between patients having MOAB and OAB alone. Four studies were included in this analysis, two RCTs (n = 709) and two cohort studies (n = 22 774), with no difference in the incidence of SSI between these groups overall or when the RCTs and cohort studies were considered separately. So, the use of OAB alone does seem to reduce SSI by at least an equivalent level to MOAB. This is reinforced by a further comparison considering OAB alone vs no preparation in two cohort studies including 16 390 patients with SSI reduced in the OAB group (relative risk 0.56, 95% CI 0.38–0.83, P = 0.004). In the Netherlands, a cohort study assessing OAB alone as standard of care over time was able to demonstrate a 6.2% reduction in deep SSI and/or mortality, which equated to a 42% risk reduction 88. The authors question the benefit of MBP in addition to OAB and are running the PreCaution study to assess whether use of OAB alone is sufficient 89. There is little Level 1 evidence for OAB alone, so should we wait to change practice until ongoing RCTs report? The first Level 1 evidence including a no bowel preparation arm is the report of the MOBILE study 45. Patients undergoing colonic, but not rectal, surgery were randomized 1:1 to MOAB or no bowel preparation. Of the 417 patients randomized, there was no difference in the primary end-point of SSI at 30 days postoperatively (7% vs 11%, odds ratio 1.65, 95% CI 0.80–3.40, P = 0.17). In the MOBILE study, low SSI rates may have been due to a high proportion of laparoscopic resections, high case exclusion rate, and more than 50% of resections being right-sided, with the suggestion that the low SSI rates may have meant it was underpowered 90, 91. However, this study does not address the issue of whether OAB alone reduce SSI. This is being examined in several large, well-powered, ongoing RCTs. The PreCaution 89, COMBINE 92 and SELDDEC trials include both colon and rectal resections; the REaCT-NSQIP and COLONPREP trials examine colonic resection alone. These large trials will provide further evidence about the role of OAB alone. However, the inclusion of both colon and rectal resections together introduces heterogeneity and possible difficulty with interpretation as OAB alone may be preferred in colonic surgery and MOAB in rectal surgery 93. However, the use of MOAB in rectal surgery will be addressed by the PREPACOL2 study. There is also a concern that these trials will end up being underpowered as they assume SSI rates in the control arms in the region of 15% and aim to show a 40%–50% reduction in primary outcome with the intervention. As SSI rates fall more widely, due to better awareness and control of SSI risk factors, the statistical assumptions on which the power calculations are based will be challenged. The relative benefit on SSI of MOAB or OAB alone, if proven, may only be small within the context of well-implemented SSI reduction bundles. The choice of antibiotics to be employed for MOAB or OAB prophylaxis is unclear. Huge numbers of antibiotics and antibiotic combinations have been employed in clinical trials. The Cochrane review of antimicrobial prophylaxis in colorectal surgery identified 68 different antibiotics in the 260 trials included. The use of multiple different drugs, regimes and site of application, including intraluminal 94, make it impossible to conclude if any regime is better or worse than any other. It does, though, appear clear that combination of aerobic and anaerobic cover is important. Concerns about excessive and widespread use of antibiotics leading to antibiotic resistance have led to programmes such as ‘Start Smart and then Focus’ within the UK 95. Despite guidelines, national surveys show that adherence to surgical prophylaxis is poor, both in timing and duration 96. As well as concerns for antibiotic stewardship, the widespread reintroduction of MOAB or OAB alone in elective colorectal surgery may have unintended consequences on the human microbiome, although this may be offset by a subsequent reduction in the use of broad spectrum antibiotic courses to treat SSI. The human large bowel microbiota comprises a consortium of many hundreds of bacterial species that carry out an array of enzymatic reactions, many distinct but essential to human genome encoded activities. In essence, therefore, humans possess an ‘extended genome’ of hundreds of millions of microbial genes located in the intestine, known as ‘the microbiome’ 97. The microbiome is highly individualized and niche specific, which may in itself explain much of the conflicting data from both MBP and MOAB trials. We have limited mechanistic data to explain how MOAB actually reduce SSI rates, as almost all prospective trials have completely failed to account for the microbiome and its functions. Recent data suggest that the commensal bacterium Enterococcus faecalis contributes to the pathogenesis of AL through its capacity to degrade collagen and to activate tissue matrix metalloproteinase 9 in host intestinal tissues 98. The conclusion of this work does not support the wholesale destruction of the gut microbiome, but rather a precision guided approach that knocks down specific strains or their functions at the site of surgical pathology. Antibiotics have a dramatic and long standing impact on both the structure and function of the gut microbiome that lasts well beyond the surgical intervention 99. By fundamentally altering (perhaps permanently) the gut microbiome with MOAB or OAB in the context of surgery it is possible that we are inadvertently modifying patient response to adjuvant therapy 100 and drug metabolism 101-103, adversely influencing their risk of non-communicable disease, drug toxicity, or even irrevocably altering gut function that may have a deleterious impact on quality of life. Currently, none of these end-points is measured in MOAB trials. While massive destruction of a complex and delicate ecosystem vital for human health and recovery from surgery should not be undertaken without careful consideration as it may have unpredictable consequences that lead to patient harm, it needs to be balanced against the reduced use of broad spectrum therapeutic antibiotics to treat SSI. Moving forwards, choice of bowel preparation must adopt a personalized strategy that promotes the beneficial behaviours of an individual’s commensal organisms and suppresses pathobionts that drive surgical complications 90, 104. Conclusion There is strong evidence that SSI reduction bundles are effective and should be used routinely in the elective colorectal surgery pathway. Colorectal units should monitor SSI rates and implementation of SSI bundles should be audited while aspiring to the low SSI rates known to be achievable from published work. There is a large and increasing body of evidence showing that MOAB are associated with reduced SSI and other postoperative complications but the quality of this evidence and its subsequent weighting is debated. It is possible that any observed effect on reduced SSI rates may be due simply to the use of OAB alone rather than MOAB. It is conceivable that, in time, OAB may be preferred in colonic surgery and MOAB in rectal resections. Informing patients of the possible benefits and risks and involving them in shared decision-making to use OAB or MOAB is recommended as best current practice due to the considerable uncertainty that persists. Emerging research focusing on the microbiome is likely to guide more personalized and specific bowel preparation regimes which will target reduction of both AL and SSI. It is imperative that clinicians contribute to ongoing research and offer their patients the opportunity to participate in high quality research studies designed to fill the existing knowledge gaps. Whilst there is much that is still unknown, the use of MOAB appears to be safe and could reasonably be used as part of an audited SSI reduction bundle, with the caveat that its use may need to be adjusted as results of ongoing high quality research emerge. Acknowledgements This topical debate paper was commissioned by the President and Executive of the Association of Coloproctology of Great Britain and Ireland. ACPGBI also funded the open access publication fee. The authors would like to thank Miss N. Fearnhead for her support in developing this debate article. Conflicts of interest No conflict of interest: SE Duff, CLF Battersby, RJ Davies, L Hancock, J Pipe, S Buczacki, J Kinross, C Walsh. AG Acheson: in the last 3 years my research department has received grant support from Pharmacosmos, Denmark and Vifor Pharma, Switzerland. Honoraria or travel support received for lecturing from the following companies: Olympus, Essex, UK, Vifor Pharma Ltd, Glattbrugg, Switzerland, and Pharmacosmos, Denmark. References 1Young H, Knepper B, Moore EE et al. Surgical site infection after colon surgery: National Healthcare Safety Network risk factors and modeled rates compared with published risk factors and rates. J Am Coll Surg 2012; 214: 852– 9. CrossrefPubMedWeb of Science®Google Scholar 2Chen M, Song X, Chen LZ et al. 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AIM:The study reports the longer-term results of laparoscopic-assisted restorative proctocolectomy (RPC), with particular reference to safety and the level of the stapled ileal pouch-anal anastomosis (IPAA).METHOD:Data were collected prospectively from all patients who underwent laparoscopic RP from July 2006 to July 2010. In each patient the operation involved the use of a short (6 cm) Pfannenstiel incision to facilitate placement of the linear stapler for anorectal division.RESULTS:Seventy-five patients underwent RPC either with total proctocolectomy (n = 53) or after previous emergency colectomy (n = 22). Early postoperative morbidity occurred in 18 (24%) patients and readmission within 30 days occurred in 18 (24%). Morbidity during follow up developed in 29 (39%). A pouchogram was carried out in all 75 patients before ileostomy closure with an abnormality shown in eight. The median level of the IPAA was at 3.0 cm (1.0-5.0 cm) above the dentate line. At a median of 33 (9-57) months, there has been one case of small bowel obstruction and no incisional hernia.CONCLUSION:In laparoscopic-assisted RPC a limited Pfannenstiel incision allows safe construction of the IPAA at an appropriate level. Laparoscopic RPC is safe and the emerging long-term follow-up data show the benefit of this approach, with very low rates of small bowel obstruction and incisional hernia formation.

Laparoscopic surgery has an expanding role in the management of colorectal disease. As technical expertise has increased, selection of patients for laparoscopic procedures has widened without any commensurate increase in operative or postoperative complications. This article aims to summarise the current status of laparoscopic surgery in colorectal disease with particular reference to colorectal cancer, inflammatory bowel disease, diverticular disease and disorders of the pelvic floor.

OBJECTIVE:Microvessel density (MVD) has been studied as a prognostic marker in human cancers. Quantification of lymphatic vessel density (LVD) is now possible by using new antibodies. Expression of the lymphangiogenic growth factors, VEGF-C and VEGF-D, is associated with poorer clinicopathological outcomes in various tumours. The aim of this study was to quantify LVD and MVD in colorectal cancer, determine the relationship between LVD, MVD and clinicopathological variables and examine the relationship between LVD and tumour expression of VEGF-C and VEGF-D.METHOD:Thirty primary colorectal cancers were immunostained for CD34, lymph vessel endothelial hyaluronan receptor-1 (LYVE-1), VEGF-A and VEGF-D using standard techniques. LVD and MVD were determined by Chalkley grid counting. Tumours were assessed for the presence or absence of LYVE-1 positive lymphatics at different areas within the tumour and the tumour was scored for VEGF-C and VEGF-D immunostaining intensity at the invading tumour edge. Non-parametric tests were used for statistical analysis and a P-value of <0.05 was taken as significant.RESULTS:Lymph vessel endothelial hyaluronan receptor-1 was an excellent lymphatic vessel marker. Within normal bowel wall, lymphatic vessels were found rarely in the superficial colonic mucosa, but were numerous in the submucosa and muscularis propria. In the majority of tumours, lymphatic vessels were located in the peri-tumoural area, intra-tumoural vessels were sparse and tended to be narrow with closed lumina. At the invading tumour edge, VEGF-C expression was higher (P = 0.028) and VEGF-D expression lower (P = 0.011), in tumours in which lymphatic vessels were present. No significant differences between LVD and any clinicopathological variable or route of metastasis were identified.CONCLUSION:Lymphatic vessel density and MVD can be quantified in colorectal carcinoma using immunohistochemical techniques. The balance between expression of VEGF-C and VEGF-D at the invading tumour edge may enhance lymphatic metastasis, by promoting tumour lymphangiogenesis or by activation of pre-existing lymphatic vessels. No relationship was identified between LVD and clinicopathological variables.

PURPOSE:Some data have suggested that major surgery is associated with the post-operative growth of residual tumour masses but the mechanism of this is unknown. This study was designed to determine the relationship between intraperitoneal (IP) cytokine levels, and laparotomy in benign and malignant settings. METHODS:Intraperitoneal fluid specimens were obtained at the start and at the end of laparotomy in patients with benign conditions (n=10) and in others undergoing resection of hepatic metastases from colorectal cancer (n=10). Using ELISA the concentration of the angiogenic cytokines, HGF, VEGF-A, VEGF-C, VEGF-D and FGF-2 was determined. RESULTS:The data show that in 16 of 20 patients there was a significant increase (P=0.006) in the IP concentration of hepatocyte growth factor (HGF) but not in the other growth factors by the end of the operation. The mean increase in HGF concentration was 821.5 pg/ml (95% CI: 11.0-6,426.0). Neither the groups (malignant and non-malignant) nor the length of operation correlated with greater or lesser increases in HGF. CONCLUSION:The observation that the increase in HGF occurred in both the cancer and non-cancer groups suggests that it is the surgery rather than the disease that is associated with the increased cytokine concentration. As HGF is a potent endothelial, epithelial and mesenchymal mitogen the data highlight HGF as a potential target for anti-cancer treatments in the peri-operative period. However, investigators should closely monitor wound healing as this may be compromised by this new class of drugs.

The structure of the neutral title complex, [{Fe[(SCH2CH2)3N](CO)2-S,S′}NiCl{[P(C6H5)2]2(CH2)3}]·CH3CN or [FeNi(C6H12NS3)Cl(C27H26P2)(CO)2]·C2H3N, is described. There are two independent complex mol­ecules and two solvent mol­ecules in the asymmetric unit. The Fe atoms are octa­hedrally coordinated; the three S atoms and a C atom of one of the two CO ligands form the equatorial plane, with the N atom of the (SCH2CH2)3N ligand and the second carbonyl C atom lying in the axial positions. The Ni atoms are square pyramidally coordinated, with the two bridging S atoms and the P atoms of the 1,3-bis­(diphenyl­phosphino)propane ligand forming the basal plane and the Cl atom lying in the apical position.

Aims: Vascular endothelial growth factor (VEGF)-C and VEGF-D are angiogenic and lymphangiogenic members of the VEGF family of growth factors. Increased VEGF-C or VEGF-D expression in human tumours may be associated with lymph-node metastasis and lymphatic invasion. Circulating plasma levels of VEGF-A, VEGF-C and VEGF-D were measured in patients with colorectal cancer, and assessed for their usefulness as a diagnostic tool for determining lymph-node metastasis.Materials and methods: One hundred and twenty patients with colorectal cancer and 50 healthy control patients were included in the study. Plasma growth-factor levels were assessed by enzyme-linked immunosorbent assays.Results: No significant differences in plasma VEGF-C or VEGF-D levels were seen between patients subgrouped by clinicopathological variables. In particular, there were no differences in median plasma VEGF-C or VEGF-D level in patients with and without lymph-node involvement (VEGF-C: 11.2 U/ml [range, 4.9-51.9] vs 9.9 U/ml [4.4-93.4 U/ml]; P = 0.90; VEGF-D: 335 pg/ml [113-1102] vs 316.5 pg/ml [0-1343]; P = 0.68).Conclusions: Circulating plasma levels of VEGF-C and VEGF-D do not allow pre-operative identification of lymph-node status in patients with colorectal cancer. (c) 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

AIM:Some of the rare complications reported in patients with an ileopouch anal anastomosis (IPAA) after coloectomy for chronic ulcerative colitis are dysplasia and carcinoma. The supposed pathway is for the ileal pouch mucosa to go through adaptational changes then is to progress through the phases of chronic pouchitis, dysplasia and subsequently to adenocarcinoma. In many of these studies however, the dysplasia-cancer sequence is inconclusive since the carcinoma might have developed from the ileal mucosa itself or from residual viable rectal mucosa left behind. The purpose of this study was therefore to study the long-term ileal mucosal adaptation patterns and the incidence and grading of dysplasia in the ileal pouch mucosa in patients previously operated on for ulcerative proctocolitis.PATIENTS AND METHODS:Forty-five patients who had been operated on with an IPAA (25 males/20 females), with a median age of 54 years (range 34-76), were invited for clinical examination and pouch endoscopy including mucosal biopsies. The duration of their colitis until surgery was median 6 years (range 1-28) and the time median interval from start of disease until time of follow up 24.8 years (range 17-46). Three independent pathologists from two different centres reviewed sequential mucosal biopsies taken from separate sites of the pouch for dysplasia and mucosal adaptation patterns.RESULTS:The type C pattern with a severe inflammation in lamina propria together with severe atrophy of villi, sometimes with ulceration and granulation tissue, was observed by the two pathologists from one centre in 15 of 45 (33.3%) patients and in 11 (24.4%) of 45 by the third pathologist, respectively. As regards dysplasia one pathologist group evaluated 2/45 (4.4%) cases as low-grade dysplasia while the third pathologist considered one of these cases as indefinite for dysplasia and one as reactive. There was in this respect full agreement between the two centres in 43 (95.6%) of 45 cases. Neither high-grade dysplasia nor invasive carcinoma was diagnosed.CONCLUSION:Dysplastic transformation within the ileal pouch mucosa in patients operated for ulcerative proctocolitis is rare even after a long follow-up. These results are reassuring for both patients and surgeons. There seem to be no solid grounds to support routine surveillance for dysplasia in the ileal pouch mucosa in these patients. The surveillance for neoplastic changes in the remaining muscular/epithelial cuff is a separate issue however.

An interim goal of the NHS National Cancer Plan is that, by 2005, patients with cancer should be treated within one month of diagnosis and within two months from urgent general practitioner referral. Preoperative radiotherapy for rectal cancer reduces the risk of local recurrence and may translate into improved patient survival. We conducted a prospective audit of existing waiting times for preoperative radiotherapy experienced by 65 patients with rectal cancer referred to the Christie Cancer Centre, Manchester, UK, between May and November 2002. The median time between referral from the surgeon to the start of radiotherapy was 40 days (range 11-85). Only 4 patients (6%) received radiotherapy within 28 days of referral by the surgeon. 62 patients (95%) underwent surgery within 14 days of completing radiotherapy. Delays in the provision of preoperative radiotherapy were primarily due to shortages of radiography staff and equipment. Lack of such infrastructure will prove a major stumbling block to achieving the targets of the NHS Cancer Plan.

Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are members of the VEGF family of cytokines and have angiogenic and lymphangiogenic actions. In gastric adenocarcinoma, VEGF-C mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis and in some reports, venous invasion and reduced 5-year survival. Patients with gastric adenocarcinomas containing high levels of VEGF-C expression have significantly reduced 5-year survival rates, and VEGF-C expression is an independent prognostic risk factor for death. The role of VEGF-C in oesophageal squamous and colorectal cancer and VEGF-D in colorectal cancer is not clear, with conflicting reports in the published literature. In order to exploit potential therapeutic applications, further research is necessary to define the precise roles of these cytokines in health and disease.

Vascular endothelial growth factor (VEGF)-C is a member of the VEGF family. VEGF-C is involved in developmental lymphangiogenesis and may be important in pathological lymphangiogenesis, lymphatic invasion and metastasis in carcinoma. We describe the development of an indirect enzyme-linked immunosorbent (ELISA) assay for the quantification of VEGF-C in plasma. Capture of VEGF-C was achieved using goat anti-human VEGF-C antibody, followed by detection with rabbit anti-human VEGF-C antibody. The sensitivity of the assay was amplified using the biotin-avidin and enhanced chemiluminescence (ECL) systems. The assay was highly sensitive and reproducible with a detection range of 0.4-100 U/ml and the intra- and inter-assay variations were less than 8%. Substitutional tests demonstrated that the assay was specific for VEGF-C with no cross-reaction with VEGF-A or VEGF-D. Practical application of the assay was evaluated in 41 colorectal cancer patients and 31 controls. Median plasma levels of VEGF-C were 35.0 U/ml (range: 17.4-75.9 U/ml) in colorectal cancer patients in contrast to 11.5 U/ml (range: 5.4-21.5 U/ml) in controls (p<0.001). Moreover, VEGF-C levels tended to be elevated in patients with advanced disease compared to early disease, but this was not statistically significant owing to a relatively small number of patients in each group. Immunoprecipitation and immunoblotting confirmed detection of VEGF-C in plasma and revealed that two forms of VEGF-C were present in the plasma corresponding to &SIM;40 and &SIM;80 kDa. The measurement of plasma VEGF-C offers opportunities to explore clinical applications in the management of malignancy, in particular in the prediction of lymphatic spread and in other lymphangiogenesis-related diseases.

CD105 and its ligand transforming growth factor β (TGF β ) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40–9.00) and 3.10 (range 0.90–8.00), respectively. Kaplan–Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGF β 1 and TGF β 3 together with the receptor–ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGF β 1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGF β 1 level was noted in patients with carcinoma over the controls. Furthermore, TGF β 3 and CD105/TGF β 3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGF β 1 was expressed in cancer cells but TGF β 3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGF β 1, TGF β 3 and CD105/TGF β complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

Formation of an ileo-anal pouch is an accepted technique following colectomy in the surgical management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The configuration of pouches and anastomotic techniques has varied over the last two decades. The increased use of stapling devices in formation of the pouch-anal anastomosis avoids the need for endoanal mucosal stripping and may contribute to improved functional results, but leaves a 'columnar cuff' of residual rectal mucosa in situ. Concerns regarding the long-term safety of the ileo-anal pouch have been raised by reports of the occurrence of dysplasia in the pouch mucosa and 15 cases of adenocarcinoma. In UC, persistence of underlying disease in the residual rectal mucosa, anal transition zone and columnar cuff provides the site for development of dysplasia and malignancy. Pouchitis is unlikely to be a major cause of dysplasia or malignancy, as long-term follow-up of patients with Koch pouches has demonstrated. In FAP, any persistent rectal mucosa and mucosa of the small intestine is at risk of adenomatous dysplasia due to the genetic alterations causing the disease. Long-term surveillance should focus on all FAP pouch patients, and in UC patients should be directed towards the diagnosis of residual rectal mucosa in the area distal to the pouch anastomosis. Specialist histopathological opinion is essential in the diagnosis of dysplasia in the ileo-anal pouch.

Debate exists about the benefits of laparoscopic appendicectomy when compared to a conventional open procedure. The majority of appendices are removed by the open route in the UK. We report a series of 132 cases of suspected appendicitis managed laparoscopically: 112 (85%) of the patients had acute appendicitis, the remaining 20 (15%) had non-appendiceal pathology. The median operative time was 30 min and there were no conversions to an open operative procedure. The median postoperative stay was two days. Complications were seen in two patients. The published evidence comparing laparoscopic and open appendicectomy is contradictory. Our series shows that laparoscopic appendicectomy is a safe procedure with low morbidity; it is also an excellent training tool in laparoscopic technique and, with sufficient experience, takes no longer than an open procedure. Negative appendicocecotomies are most common in women of fertile age and can be associated with significant morbidity; therefore, laparoscopy should be used to make the diagnosis and, if appendicitis is the cause, the appendix could safely be removed laparoscopically. However, the choice between open and laparoscopic procedure is a subjective decision for the patient and their surgeon. Laparoscopic appendicectomy cannot be regarded as the gold standard.

The treatment of cervical fixed flexion deformity in ankylosing spondylitis presents a challenging problem that is traditionally managed by a corrective cervicothoracic osteotomy. The authors report a new approach to this problem that involves performing a two-level osteotomy at the level of maximum spinal curvature, thereby achieving complete anatomical correction in a one-stage procedure.This 48-year-old woman with ankylosing spondylitis presented with a 30-year history of progressive neck deformity that left her unable to see ahead and caused her to experience difficulty eating, drinking, and breathing on exertion. On examination, she exhibited a 90 degrees fixed flexion deformity of the cervical spine, which was maximum at C-4; this was confirmed on imaging studies.A two-level osteotomy was performed at C3-4 and C4-5 around the area of maximum spinal curvature, and the deformity was corrected by extending the head on its axis of rotation through the uncovertebral joints. The spine was stabilized using a Ransford loop. An excellent anatomical position was achieved, as was complete correction of the deformity.A two-level midcervical osteotomy performed at the level of maximum spinal curvature in ankylosing spondylitis enables complete correction of severe fixed flexion deformity in a single procedure. Preservation of the uncovertebral joints allows smooth and safe correction of the deformity about their axis of rotation.

Surgeons face the occupational risk of parenteral transmission of infection, in particular with HIV, percutaneous exposure to which carries an estimated risk of transmission of 0.3%.1–3 This risk may be reduced by antiretroviral prophylactic treatment.4 The UK Department of Health issued guidelines on post-exposure prophylaxis in June 1997.5 We assessed whether the guidelines had been implemented and whether surgeons were aware of them in the South and West health region.We conducted a telephone survey of all the occupational health departments and on-duty general surgical and orthopaedic registrar grade surgical trainees in the South and West region. Separate sets of questions were used for occupational health departments and surgical trainees (box).#### Survey questions##### To both groups