The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. 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 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Hughes Abdominal Repair Trial (HART) - Abdominal wall closure techniques to reduce the incidence of incisional hernias: study protocol for a randomised controlled trial.

BACKGROUND: Incisional hernias are common complications of midline closure following abdominal surgery and cause significant morbidity, impaired quality of life and increased health care costs. The 'Hughes Repair' combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. This theoretically distributes the load along the incision length as well as across it. There is evidence to suggest that this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared the Hughes Repair with standard mass closure for the prevention of incisional hernia formation following a midline incision. METHODS/DESIGN: This is a 1:1 randomised controlled trial comparing two suture techniques for the closure of the midline abdominal wound following surgery for colorectal cancer. Full ethical approval has been gained (Wales REC 3, MREC 12/WA/0374). Eight hundred patients will be randomised from approximately 20 general surgical units within the United Kingdom. Patients undergoing open or laparoscopic (more than a 5-cm midline incision) surgery for colorectal cancer, elective or emergency, are eligible. Patients under the age of 18 years, those having mesh inserted or undergoing musculofascial flap closure of the perineal defect in abdominoperineal wound closure, and those unable to give informed consent will be excluded. Patients will be randomised intraoperatively to either the Hughes Repair or standard mass closure. The primary outcome measure is the incidence of incisional hernias at 1 year as assessed by standardised clinical examination. The secondary outcomes include quality of life patient-reported outcome measures, cost-utility analysis, incidence of complete abdominal wound dehiscence and C-POSSUM scores. The incidence of incisional hernia at 1 year, assessed by computerised tomography, will form a tertiary outcome. DISCUSSION: A feasibility phase has been completed. The results of the study will be used to inform current and future practice and potentially reduce the risk of incisional hernia formation following midline incisions. TRIAL REGISTRATION NUMBER: ISRCTN 25616490 . Registered on 1 January 2012.

Do classroom ventilation rates in California elementary schools influence standardized test scores? Results from a prospective study.

Limited evidence has associated lower ventilation rates (VRs) in schools with reduced student learning or achievement. We analyzed longitudinal data collected over two school years from 150 classrooms in 28 schools within three California school districts. We estimated daily classroom VRs from real-time indoor carbon dioxide measured by web-connected sensors. School districts provided individual-level scores on standard tests in Math and English, and classroom-level demographic data. Analyses assessing learning effects used two VR metrics: average VRs for 30 days prior to tests, and proportion of prior daily VRs above specified thresholds during the year. We estimated relationships between scores and VR metrics in multivariate models with generalized estimating equations. All school districts had median school-year VRs below the California VR standard. Most models showed some positive associations of VRs with test scores; however, estimates varied in magnitude and few 95% confidence intervals excluded the null. Combined-district models estimated statistically significant increases of 0.6 points (P = 0.01) on English tests for each 10% increase in prior 30-day VRs. Estimated increases in Math were of similar magnitude but not statistically significant. Findings suggest potential small positive associations between classroom VRs and learning.

A case-control study of risk factors for wound infection in a colorectal unit.

INTRODUCTION: Postoperative wound infections have been responsible for increasing morbidity and are associated with an increased use of hospital resources. Previous studies have identified several risk factors. However, most studies are outdated, and few relate to the era of enhanced recovery and laparoscopic surgery. This study investigated the association between patient and operative factors and the development of postoperative wound infections in colorectal surgery. METHODS: Patients with documented wound infections or dehiscences were identified from a database of elective and emergency colorectal surgery. Patients with wound infections were matched by operation type to a control group of colorectal patients. Differences in patient and operative factors between case and control group were analysed using conditional logistic regression. RESULTS: A total of 56 patients with wound infection were identified from 647 operations (8.6%). Fifty-seven per cent were emergency operations and eighty-eight per cent were performed as open surgery or as laparoscopic surgery converted to open. Forty per cent of patients had high ASA (American Society of Anesthesiologists) grades (3 or 4). Multivariate logistical regression showed that obese patients and those having open surgery had the highest risk of infections. The median postoperative hospital stay for patients with wound infections was twice as long as for those patients without wound infections. CONCLUSIONS: Open surgery and obesity are independent risk factor for wound infections. An increase in laparoscopically performed operations and new strategies for managing wounds in obese patients may help to reduce the rate of wound infection.

Association of classroom ventilation with reduced illness absence: a prospective study in California elementary schools.

Limited evidence associates inadequate classroom ventilation rates (VRs) with increased illness absence (IA). We investigated relationships between VRs and IA in California elementary schools over two school years in 162 3rd-5th-grade classrooms in 28 schools in three school districts: South Coast (SC), Bay Area (BA), and Central Valley (CV). We estimated relationships between daily IA and VR (estimated from two year daily real-time carbon dioxide in each classroom) in zero-inflated negative binomial models. We also compared IA benefits and energy costs of increased VRs. All school districts had median VRs below the 7.1 l/s-person California standard. For each additional 1 l/s-person of VR, IA was reduced significantly (p<0.05) in models for combined districts (-1.6%) and for SC (-1.2%), and nonsignificantly for districts providing less data: BA (-1.5%) and CV (-1.0%). Assuming associations were causal and generalizable, increasing classroom VRs from the California average (4 l/s-person) to the State standard would decrease IA by 3.4%, increase attendance-linked funding to schools by $33 million annually, and increase costs by only $4 million. Further increasing VRs would provide additional benefits. These findings, while requiring confirmation, suggest that increasing classroom VRs above the State standard would substantially decrease illness absence and produce economic benefits.

Role of mitochondria in contraction and pacemaking in the mouse uterus.

BACKGROUND AND PURPOSE: Uterine spontaneous contraction and pacemaking are poorly understood. This study investigates the role of the mitochondrial Ca(2+) store in uterine activity. EXPERIMENTAL APPROACH: We investigated the effects of mitochondrial and sarco-endoplasmic reticulum (SER) inhibitors on contraction, membrane potential (Vm) and cytosolic Ca(2+) concentration ([Ca(2+) ](c) ) in longitudinal smooth muscle of the mouse uterus. KEY RESULTS: The mitochondrial agents rotenone, carbonylcyanide-3-chlorophenylhydrazone (CCCP), 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157) and kaempferol decreased the force of contractions. The ATP synthase inhibitor oligomycin had no significant effect. The effects of these agents were compared with those of SER inhibitors cyclopiazonic acid (CPA), 2-amino ethoxyphenylborate (2-APB) and caffeine. All agents, except CPA and oligomycin, decreased contractile force. CPA and CCCP transiently increased contraction frequency, which returned to control levels, whereas rotenone, CGP37157, kaempferol and 2-APB decreased frequency and caffeine had no significant effect. Application of the mitochondrial agents when CPA functionally inhibited stores did not change contraction frequency but, with the exception of kaempferol, decreased force. CCCP caused depolarization and maintained increase in [Ca(2+) ](c) or depolarization/transient hyperpolarization and transient increase in [Ca(2+) ](c) for oestrus and di-oestrus tissues respectively. Rotenone caused hyperpolarization and maintained increase in [Ca(2+) ](c) . CGP37157 and kaempferol caused hyperpolarization but no measurable change in [Ca(2+) ](c) . Application of a range of K(+) channel blockers indicated a role of Ca(2+) -activated K(+) (K(Ca) ) channels in the CCCP- and CGP37157-induced actions. CONCLUSIONS AND IMPLICATIONS: Mitochondria have a modulatory role on uterine contractions, with mitochondrial inhibition reducing contraction amplitude and pacemaker frequency by changes in Vm, [Ca(2+) ](c) and/or Ca(2+) influx.

Management of the asymptomatic primary in the palliative treatment of metastatic colorectal cancer.

OBJECTIVE: The management of the asymptomatic primary in stage IV colorectal cancer presents a dilemma. There is an increased morbidity and mortality from surgical resection. Nonresectional management of the primary is associated with the risks of obstruction, perforation or haemorrhage. Our practice in patients with stage IV disease is palliative chemotherapy and symptom control. We reviewed our nonoperatively managed patients with colorectal liver metastases in order to identify the percentage of patients requiring urgent operative interventions for symptoms related to the primary. SUBJECTS/PATIENTS AND METHOD: A retrospective review of all patients treated for stage IV disease at our institution from 2003-2006 was undertaken. Patients were identified from multidisciplinary team (MDT) records. Demographic detail, treatment, and follow-up data were extracted from hospital records. These were analysed with Microsoft Excel. RESULTS: Thirty-seven patients were identified. 26 Male:11 Female. Median age 63 years (range 38-78). The median survival from diagnosis was 14 months. Three (8%) patients developed obstruction whilst having palliative chemotherapy. Two required a defunctioning stoma, and one was treated by means of a stent. There were no similarities between these three patients in terms of age, sex, site or stage of primary, volume of liver metastases, and alkaline phosphatase (ALP) or carcinoembryonic antigen (CEA) levels. CONCLUSION: Of 37 patients initially treated palliatively for stage IV colorectal cancer, 92% required no surgical treatment of their primary. Therefore it is the experience of this MDT that it is acceptable to treat such patients in an expectant manner. It is not possible to predict those patients, likely to require surgical intervention.

Laparoscopic surgery for colorectal cancer: the state of the art.

Laparoscopic techniques have expanded since their introduction 15 years ago. The laparoscopic approach for colorectal surgery has been slower to develop than other fields of surgery. However, this approach does provide significant benefits for colorectal resection, although concerns regarding the ability to satisfy oncological criteria have restricted its use in the past. This review studies the published data on the use of laparoscopic surgery for colorectal cancer including the short- and long-term outcomes. New long-term outcome data is now available which is likely to encourage the use of this technique for colon cancer resection. Laparoscopic rectal cancer resection is also discussed including the more limited outcome data that is available.

Bacillus anthracis contamination and inhalational anthrax in a mail processing and distribution center.

AIMS: Four inhalational anthrax cases occurred in a large mail processing and distribution center in Washington, DC, after envelopes containing Bacillus anthracis spores were processed. This report describes the results of sampling for B. anthracis spores during investigations conducted in October and December 2001. METHODS AND RESULTS: Wet swabs, wet wipes, vacuum sock, and air-filter samples were collected throughout the facility to characterize the extent of building contamination. The results showed widespread contamination of B. anthracis spores, particularly associated with one delivery bar code sorter (DBCS) machine that had sorted the spore-containing envelopes and an area where the envelopes were handled by postal workers. Spore concentrations decreased as distance from the DBCS machine increased, but spores were widely dispersed into surrounding areas. CONCLUSION: The spatial distribution of culture positive samples was closely related to the work areas of the inhalational anthrax cases and supported epidemiological evidence that the workers became ill from exposure to B. anthracis spores in areas where the contaminated envelopes had travelled. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this investigation were used to guide decontamination efforts and provided baseline spore concentrations for follow-up measurements after the building had been cleaned. Implementing methods to reduce aerosolization and dispersion of dust within the facility would reduce postal workers' potential exposures to bioterrorism agents.

3D GPS mapping of land contaminated with gamma-ray emitting radionuclides.

Two studies are given in this paper. Both studies use a combined gamma sensing and global positioning system to monitor land contaminated with gamma emitting radioisotopes. The first is the 3D profiling a large (100m x 200m x 15m) tip of the residue from radium extraction processing. The second is the dynamic monitoring of beaches to locate and recover small particles of radioactive material.

Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model.

One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential.

Continuous angiotensin II infusion increases tumour: normal blood flow ratio in colo-rectal liver metastases.

Insufficient blood flow within colo-rectal hepatic metastases is a factor which may limit drug delivery to, and thus the response of, these tumours to regional chemotherapy. Loco-regional flow may be manipulated pharmacologically to enhance the tumour blood flow relative to that of the normal liver. However, as yet, only transient effects have been studied. Patients receiving regional chemotherapy for unresectable hepatic disease were given a 45 min regional infusion of the vasoconstrictor Angiotensin II. Intrahepatic blood flow distribution was assessed serially by Positron Emission Tomography (PET) imaging together with the trapping tracer copper(II) pyruvaldehyde bis(N-4-methylthiosemicarbazone) (Cu-PTSM) labelled using copper-62. Eleven lesions in nine patients were studied, with no adverse effects. Prior to Angiotensin II administration tumour blood flow was generally found to be greater than that of liver (10/11 lesions; 8/9 patients; median TNR 1.3, iqr 0.9-2.5). A significant increase in relative flow to tumour was seen in response to 10 min Angiotensin II infusion in most cases (7/11 lesions; 7/9 patients; median TNR 2.1, iqr 1.4-4.1; P = 0.008), which appeared to be sustained throughout the 45 min infusion period (median TNR 1.85, iqr 1.3-3.8; P = 0.03). These effects were accompanied by transient elevation of mean arterial pressure, but no change in pulse rate. These observations suggest that prolonged regional vasoconstrictor administration could prove useful in the management of unresectable colo-rectal hepatic metastases, and that further development of vascular manipulation to enhance tumour targeting and drug delivery is warranted.

The maternity information concerns of Somali women in the United Kingdom.

AIMS: The aims of the study were to explore the maternity information concerns of a group of Somali women in a Northern English city and to investigate the relationships of these women with maternity health professionals. BACKGROUND: The Somali community is one of the most established ethnic minorities in the United Kingdom (UK). The health needs of this group and in particular, the information needs of Somali women with respect to pregnancy, childbirth and post-natal care are poorly understood. To facilitate information provision to birthing mothers and to support maternal decision-making among minority ethnic women, research is required to understand and identify their information needs. METHODS: A user-centred study utilizing a focus group and semi-structured interviews with English-speaking and non-English speaking Somali women was conducted in a large English city. Discussions were audiotaped, translated, transcribed and then analysed using a variation of the constant comparative METHOD: Themes and categories were identified across transcripts during data collection and analysis and appropriate quotations are used to illustrate all themes. FINDINGS: Major findings that emerged from the analysis related to contact with health professionals, language support and information and satisfaction with health professionals. The findings indicate key maternity information concerns of Somali women with regard to maternity issues and have a number of implications for midwifery and nursing practice. CONCLUSIONS: Poor communication between the non-English speaking Somali women and health workers was perceived as an underlying problem in seeking information. Fears about misinterpretation and confidentiality, limit the usefulness of interpreters. The Somali women perceived that they were denied information due to punitive attitudes and prejudiced views among health professionals.

62Cu-PTSM and PET used for the assessment of angiotensin II-induced blood flow changes in patients with colorectal liver metastases.

The aim of this study was to establish a quantitative positron emission tomography (PET) method for investigating angiotensin II (AII)-induced changes in blood flow distribution in the liver. This was in order to evaluate the role of vascular manipulation applied to locoregional chemotherapy treatment in patients with colorectal liver metastases. The tracer selected was copper-62 (II) pyruvaldehyde bis-(N4-methyl)thiosemicarbazone (62Cu-PTSM), which exhibits high first-pass extraction and tissue retention following intra-arterial administration. The short half-life of the tracer and its availability from a 62Zn/62Cu generator enabled short-interval repeat PET scans on patients in a single imaging session. Distribution of tracer within the liver was imaged in a single view using a PET camera with rotating large-area detectors. By optimisation of the acquisition protocol, it was possible to acquire sufficient data to produce good-quality images and to quantify tracer uptake with an accuracy of <10%. Reproducibility of the imaging method was assessed in a single patient in whom three consecutive 62Cu-PTSM PET scans were obtained, and in whom no vascular manipulation was performed. Sets of scans (before, during and immediately after a 45-min AII infusion) were obtained in nine patients to assess blood flow changes associated with prolonged vascular manipulation. Significant individual responses, varying in both the magnitude and the duration of flow change, were observed in the majority of cases (7/11 lesions; 7/9 patients). These findings illustrate the potential of 62Cu-PTSM and PET for pharmacological studies. The wide range of individual patient responses to AII infusion suggests that PET blood flow assessment would be of value for selecting patients in whom this procedure may be effective.

Plasma vascular endothelial but not fibroblast growth factor levels correlate with colorectal liver mestastasis vascularity and volume.

The extent to which plasma levels of angiogenic factors in healthy individuals and tumour volume-related variations in colorectal cancer affect the accuracy of circulating angiogenic factors as predictors of colorectal cancer vascularity is unknown. We used enzyme-linked immunosorbant assay to measure plasma vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels in colorectal liver metastasis (CLM) patients, and 'no cancer' controls. CLM volume was determined from computerized tomography scans, and tumour vessel count and vessel volume from anti-endothelial antibody-stained biopsies. There was a significant (P= 0.03) increase in plasma VEGF level in 29 CLM patients (median 180.3 pg/ml(-1), iqr 132.5-284.8 pg/ml(-1) compared with 19 controls (median 125.8 pg/ml(-1), iqr 58.2-235.9 pg/ml(-1). There were significant correlations between plasma VEGF and tumour vessel count (r = 0.66, P = 0.03), tumour vessel volume (r= 0.59, P = 0.03), and CLM volume (r= 0.53, P = 0.03). A VEGF level in the upper quartile of the plasma VEGF distribution had a 70% sensitivity and 75% specificity in predicting an upper quartile liver metastasis tumour vessel count. No relation was identified between CLM and plasma bFGF levels. Plasma VEGF level predicted CLM vascularity, despite an overlap with normal levels and tumour volume-related variations.

Colorectal liver metastasis thymidylate synthase staining correlates with response to hepatic arterial floxuridine.

We assessed whether intensity of colorectal liver metastasis staining with the thymidylate synthase (TS) antibody TS106 predicted response to hepatic arterial infusion (HAI) of floxuridine chemotherapy. Liver metastasis biopsies were taken during laparotomy for hepatic arterial cannulation and stained using the TS106 monoclonal antibody. Staining intensity was designated at histological examination by two independent assessors as either "high" or "low." Patients were treated by HAI, and liver metastasis response was assessed by comparison of computed tomography scan tumor volume before and after 4 months of treatment. A significant correlation (Fisher's exact test, P = 0.01) was noted between partial response to HAI and TS106 staining intensity in patients with colorectal liver metastases. Seventy-five percent of patients with evidence of a partial response had low TS staining compared with 29% of nonresponders. There was a significant difference (Fisher's exact test, P = 0.01) in the proportion of low (9 of 16) compared with high (3 of 20) TS staining tumors in which a partial response occurred. There was no significant difference (logrank test, P = 0.4) in survival from hepatic cannulation and HAI treatment of high (median, 322 days; interquartile range, 236-411) compared with low (median, 335 days; interquartile range, 301-547) TS staining patients. This study demonstrates an inverse correlation between TS immunohistochemical staining intensity in colorectal liver metastases and response to HAI. The results suggest that a prospective assessment of TS staining intensity in colorectal liver metastases would be useful to determine whether this method can be used to define patients who will benefit from HAI chemotherapy.

Hepatic arterial floxuridine as second-line treatment for systemic fluorouracil-resistant colorectal liver metastases.

Hepatic arterial floxuridine (HAI) in 35 patients with systemic fluorouracil/folinic acid-resistant colorectal liver metastases achieved a 14% partial response and 26% disease stabilization rate, with a median response duration of 7 months from onset of HAI.

Management of symptomatic locoregional recurrence during regional chemotherapy for colorectal liver metastases.

BACKGROUND: The incidence of symptomatic locoregional recurrence is doubled in patients receiving regional chemotherapy with hepatic arterial floxuridine infusion (HAI) compared with that in those with colorectal liver metastases treated by symptom control. This study assessed the management of symptomatic locoregional recurrence in HAI-treated patients with colorectal liver metastases. METHODS: A retrospective review of all patients with colorectal liver metastases treated by HAI in one hospital over a 10-year period was carried out and the management of those who developed symptomatic locoregional recurrence was studied. RESULTS: Twenty-three (14 per cent) of 166 HAI-treated patients with colorectal liver metastases developed symptoms of locoregional recurrence. Liver metastases were responding to HAI at the onset of symptoms in 19 (ten abdominal, nine pelvic recurrence) of the 23 patients. Resection of abdominal recurrence was possible in seven of the ten patients, with a median hospital stay of 14 days; there was one perioperative death. Resected patients survived a median of 15 months after resection of the recurrence, with five of seven remaining free of symptoms of locoregional recurrence. In contrast, six of nine HAI-responding patients with pelvic recurrence treated by external beam radiotherapy died from uncontrolled symptomatic pelvic disease. CONCLUSION: Resection of abdominal recurrence achieved worthwhile palliation in patients with HAI-controlled liver metastases, but palliation of pelvic recurrence by irradiation was unsatisfactory.