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Background: The benefits of stroke volume optimization during surgery are unclear, with recent data not replicating the positive effects of earlier studies., Methods: This was a randomized controlled trial of standard fluid therapy with or without supplementary blinded intraoperative stroke volume optimization in 220 patients having major elective rectal resection or cystectomy with ileal conduit. All patients were treated using a contemporary enhanced recovery pathway. Interventional fluid challenges used Gelofusine (B Braun, Germany), guided by stoke volume variability measured by LiDCOrapid (LiDCO, UK). Participants were stratified by aerobic fitness (characterized by preoperative cardiopulmonary exercise test), surgical specialty, and intended surgical approach (open or laparoscopic). The primary outcome was the prevalence of moderate or severe complications on day 5 after surgery, defined using the postoperative morbidity survey (POMS) criteria., Results: Patients received ∼13 ml kg(-1) h(-1) of i.v. fluids during surgery. The intervention group received an additional mean (sd) 956 (896) ml Gelofusine. There were no statistically significant differences between groups in any primary or secondary end point. A positive POMS on postoperative day 5 was noted in 54 of 111 control subjects (48.6%) and 55 of 109 participants in the intervention group [50.5%; adjusted odds ratio 0.90 (95% confidence interval 0.52-1.57), P=0.717]. Mean (sd) hospital length of stay was 9.6 (6.8) days in the control group and 11.8 (11.5) days in the intervention group (adjusted difference -2.1 (-4.6 to 0.3) days, P=0.091). There was no statistical interaction between stroke volume optimization and aerobic fitness in terms of rate of complications or length of stay., Conclusions: Algorithm-driven stroke volume optimization is of no benefit when superimposed on a liberal baseline fluid regimen in patients having elective major abdominal surgery, when stratified to minimize differences in fitness and surgical approach between groups., Clinical Trial Registration: ISRCTN21597243., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Surgical patients with poor functional capacity, determined by oxygen consumption at anaerobic threshold (AT) during cardiopulmonary exercise testing (CPET), experience longer hospital stays and worse short- and medium-term survival. However, previous studies excluded patients who were unable to perform a CPET or who failed to demonstrate an AT. We hypothesized that such patients are at risk of inferior outcomes after elective surgery., Methods: All patients undergoing major colorectal surgery attempted CPET to assist in the planning of care. Patients were stratified by their test results into Fit (AT ≥ 11.0 ml O2 kg(-1) min(-1)), Unfit (AT < 11.0 ml O2 kg(-1) min(-1)), or Unable to CPET groups (failed to pedal or demonstrate an AT). For each group, we determined hospital stay and mortality., Results: Between March 2009 and April 2010, 269 consecutive patients were screened, and proceeded to bowel resection. Median hospital stay was 8 days (IQR 5.1-13.4) and there were 44 deaths (16%) at 2 yr; 26 (9.7%) patients were categorized as Unable to CPET, 69 (25.7%) Unfit and 174 (64.7%) Fit. There were statistically significant differences between the three groups in hospital stay [median (IQR) 14.0 (10.5-23.8) vs 9.9 (5.5-15) vs 7.1 (4.9-10.8) days, P < 0.01] and mortality at 2 yr [11/26 (42%) vs 14/69 (20%) vs 19/174 (11%), respectively (P < 0.01)] although the differences between Unable and Unfit were not statistically different., Conclusions: Patients' inability to perform CPET is associated with inferior outcomes after major colorectal surgery. Future studies evaluating CPET in risk assessment for major surgery should report outcomes for this subgroup.

Aim: To evaluate the clinical impact and cost-effectiveness of a multidisciplinary team (MDT) meeting in a large hospital in the UK., Materials and Methods: A management plan for colorectal cancer patients was recorded by the supervising surgical consultant prior to the MDT meeting using the available clinical information and the available reports for imaging and histopathology. The recorded outcomes were then compared with the outcomes documented at the subsequent MDT meeting. The cost of the MDT meeting was calculated based on the salaries of individuals involved plus relevant overheads. A range of opportunity costs were considered, the most significant of which was the expenditure required to re-provide direct clinical care displaced by the MDT., Results: Over a 3 month period a sample of 47 random cases were reviewed from the colorectal MDT. In three patients, there were significant differences between the preliminary consultant decision and the MDT recommendation: in one case management was changed based on further information about patient co-morbidity and performance status. In only one case was there a material alteration to a CT report, which altered management. The annual costs of running this colorectal local MDT alone were estimated at £162,734+ per annum with opportunity costs of at least twice that., Conclusion: The costs of MDT meetings are very high producing a small clinical impact. At a time of increasing financial and capacity pressure in healthcare systems, the use of scarce resources may be better deployed elsewhere., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Aim: To determine the long-term outcomes of patients in whom no initial cause for their anaemia is established., Method: Six hundred and thirty-nine patients presenting to an iron deficiency anaemia pathway were prospectively entered onto a database. Initial assessment included haematological review, coeliac screen, oesophagogastroduodenoscopy and colonic imaging as per British Society of Gastroenterology guidelines. A 5-year audit of outcomes was undertaken using patient medical records and hospital laboratory databases., Results: A diagnosis was found initially in 266 (42%) patients, with 124 (19%) having a gastrointestinal (GI) luminal neoplasm, 54 (8%) of which were malignant. Twelve patients had a nonluminal or non-GI malignancy. Eighty-eight (14%) had benign upper GI bleeding and 23 (4%) had coeliac disease. One hundred and forty-three (22%) did not have confirmed iron deficiency anaemia on review of haematinics. Complete records were available for 595 (93%) patients at 5 years. Of the 373 patients in whom a cause was not initially diagnosed, 6 (2%) were ultimately diagnosed with a GI luminal malignancy and 18 (5%) with a nonluminal or non-GI malignancy. There was no difference in the incidence of malignancies between those with or without confirmed iron deficiency., Conclusions: Most patients in whom no cause was found at initial investigation resolve on oral iron supplements. Patients with normal ferritin values had as high an incidence of GI malignancies as those with low values and should be investigated. In the over 50s if the anaemia remains after a course of iron further investigation is recommended as there is a significant incidence of both GI and non-GI pathology., (© 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.)

Background: Intraoperative fluid therapy regimens using oesophageal Doppler monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy, GDT) have been associated with a reduction in length of stay (LOS) and complication rates after major surgery. We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge (RfD) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients., Methods: In this double-blinded controlled trial, 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically 'fit' (n=123) or 'unfit' (n=56) on the basis of their performance during a cardiopulmonary exercise test. Within these fitness strata, patients were randomized to receive a standard fluid regimen with or without ODM-guided intraoperative GDT., Results: GDT patients received an average of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls. Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7 days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs 4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with controls., Conclusions: Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome., Trial Registry: UK NIHR CRN 7285, ISRCTN 14680495. http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285.

Aim: The aim of this study was to describe an easy and reproducible method of measuring clinical performance in colonoscopy., Method: Data from all endoscopy procedures performed within the main endoscopy unit at Derriford Hospital between January and December 2007 were analysed. Points were allocated for given procedures. A local health economic analysis revealed that at least 8 points (or four colonoscopies) must be performed to meet list costs. The clinical performance was described as a capability index of crude Caecal Intubation Rate (CIR) vs the mean Points Performed/Endoscopy List (points/list)., Results: Overall, 3884 colonoscopies were performed, with a mean crude CIR of 89.6% and 8.3 points/List. Only 7/23 endoscopists consistently met the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) standard in a cost-effective way. An annual colonoscopy rate of ≥ 150 cases was associated with higher points per list (points/list) (P = 0.003). Endoscopists offering ≥ 15% of cases as training cases had significantly higher crude CIRs and points/list (P = 0.051; P = 0.017)., Conclusions: Clinical performance is a function of quality provided in a cost-effective way. Our capability index is an effective and reproducible way of measuring clinical performance. Training was not associated with reduced volume., (© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.)

Background: Several instruments are available for open and laparoscopic dissection, including electrothermal bipolar vessel sealers and ultrasonically coagulating shears. The vessel sealing ability of three devices in colorectal specimens was compared in an experimental study., Methods: Surgical specimens from patients scheduled for elective open or laparoscopic colorectal resection were allocated to one of the three devices. After removal of the surgical specimen, up to eight mesenteric vessels were dissected ex vivo and sealed using the allocated instrument. The vessel seal was tested for the maximum pressure at which it leaked and then assessed by a pathologist for depth of thermal tissue damage., Results: A total of 93 vessels from 18 patients were assessed ex vivo (LOTUS™ n = 33; Harmonic Ace® n = 30; LigaSure™ n = 30), a median of 6 (range 1-8) vessels per surgical specimen with a mean(s.d.) diameter of 1·06(0·70) mm and wall thickness of 0·29(0·19) mm. Mean(s.d.) bursting pressures were 1170(440), 1470(670) and 1510(740) mmHg with LOTUS(™) , Harmonic Ace® and LigaSure™ respectively. ANCOVA showed no difference in bursting pressure between the instruments (P = 0·058). The depth of thermal damage was significantly greater with LigaSure™ (3·37(1·44) mm) than with LOTUS(™) (2·18(0·99) mm; P < 0·001) or Harmonic Ace® (1·95(0·92) mm; P < 0·001)., Conclusion: All three instruments were equally good at sealing blood vessels, with bursting pressures well above physiological blood pressure levels., Registration Number: NCT01121614 (http://www.clinicaltrials.gov)., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: The transfusion rate following colorectal cancer resection is between 10 and 30 per cent. Receipt of allogeneic blood is not without risk or cost. A preoperative adjunct that reduced the need for transfusion would mitigate these risks. This study was designed to determine whether iron sucrose reduces the likelihood of postoperative blood transfusion in patients undergoing elective colorectal cancer resection., Methods: In this randomized prospective blinded placebo-controlled trial of patients undergoing resectional surgery with a preoperative diagnosis of colorectal cancer, 600 mg iron sucrose or placebo was given intravenously in two divided doses, at least 24 h apart, 14 days before surgery. The primary outcome measures were serum haemoglobin concentration, recorded at recruitment, immediately before surgery and at discharge, and perioperative blood transfusions., Results: No difference was demonstrated between treatment groups (iron sucrose, 34 patients; placebo, 26) for any of the primary outcome measures, for either the whole study population or a subgroup of anaemic patients., Conclusion: This pilot study provided no support for the use of intravenous iron sucrose as a preoperative adjunct to increase preoperative haemoglobin levels and thereby reduce the likelihood of allogeneic blood transfusion for patients undergoing resectional surgery for colorectal cancer., Registration Number: 2005-003608-13UK (Medicines and Healthcare products Regulatory Agency).

Background: An important cause of delayed recovery from intestinal surgery is postoperative ileus. Gum chewing is a form of sham feeding, which could encourage gastrointestinal motility through cephalic-vagal stimulation., Methods: We sought to identify all randomized controlled trials comparing gum chewing with standard care after elective intestinal surgery. We searched electronic databases (Cochrane, Embase, and PubMed), reference lists and contacted authors to obtain further data. We assessed the identified trials for quality and performed a meta-analysis and systematic review. The main outcome measures examined were time to flatus and stool postoperatively and length of hospital stay, which were analysed using random effect models. We also examined clinical complication rates., Results: We identified nine eligible trials that had enrolled a total of 437 patients. The intervention was well tolerated and complication rates were low. There was statistical evidence of heterogeneity for the three main outcomes. Pooled estimates showed a reduction in time to flatus by 14 h (95% CI: -20 to -8h, p=0.001), time to bowel movement by 23 h (95% CI: -32 to -15 h, p<0.001) and a reduction in length of hospital stay by 1.1 days (95% CI: -1.9 to -0.2 days, p=0.016)., Conclusions: Chewing sugarless gum following elective intestinal resection is associated with improved outcomes. Insufficient data were available to demonstrate a reduced rate of clinical complications or reduced cost. An adequately powered, methodologically rigorous trial of gum chewing is required to confirm if there are any benefits and if these result in differences in clinical outcomes such as infection.

Purpose: Colonoscopy is the "gold standard" for assessing colonic mucosal abnormalities. An important component of this is complete examination to the cecum. However, the ability to detect abnormalities is equally important and has received less attention. This study was designed to assess the accuracy of detection of artificial bowel markers as surrogates for small polyps., Methods: Patients were randomly assigned to receive between zero and four of each of two types of marker. Markers used were 5-mmx5-mm pieces of latex-free rubber or 12-mmx1.5-mm metallic bowel clips. These were placed on insertion of the colonoscope. At the limit of the colonoscopy, a second blinded endoscopist performed the extubation. Six endoscopists took part in the study. Data regarding the number, type, and position of the markers on insertion and withdrawal were recorded as were insertion and withdrawal times., Results: A total of 179 markers (85 clips, 94 rubbers) were placed in 44 patients. The cecal intubation rate was 91 percent. Median intubation time was 20 minutes and withdrawal time was 15 minutes; 139 markers (77.7 percent) were detected on withdrawal (clips, 76.5 percent; rubbers, 78.7 percent). There was no correlation between insertion or withdrawal times and marker detection. Detection rates varied between endoscopists (71-87 percent), but there was no correlation with individual cecal intubation rates (P=0.96). Markers placed at flexures were missed more often (P=0.008)., Conclusions: Artificial markers provide a novel method for assessing colonoscopic accuracy. The results obtained with this method are closely concordant with results from other studies. The technique is potentially useful in training, audit, and future research.

Surgery is the definitive tool in the management of patients with rectal carcinoma. Early failure of treatment remains problematic and is manifest in local recurrence. Development of surgical techniques and inclusion of other treatment modalities aim to reduce the incidence of local recurrence and improve survival. This article examines the role of radiotherapy in the management of patients with rectal carcinoma and explores the controversies that exist in its application. The evidence for the use and benefits of radiotherapy in adjuvant and neoadjuvant settings is reviewed, and its application in association with total mesorectal excision considered.

Aims: The Royal College of Surgeons of England and the Association of Coloproctology of Great Britain and Ireland guidelines for the management of colorectal cancer were published in 1996. We audited our practice against these guidelines., Methods: Data from 211 consecutive patients undergoing colorectal cancer surgery, between September 1999 and September 2000, have been prospectively collected. Preoperative large bowel and liver imaging, assessment by colorectal specialist nurses and median number of lymph nodes resected have been compared between specialist colorectal and non-colorectal surgeons for rectal and colonic cancers. The adequacy of resection and rates of abdomino-perineal resection have been compared for rectal cancers. Following presentation of our findings, we re-audited practice between January and June 2002., Results: There was marked variation in practice within our hospital. Colorectal specialists were more likely to conform to best practice guidelines, performed fewer abdomino-perineal resections and tended to perform more extensive lymphadenectomy. Following presentation of these data, compliance with guidelines was markedly improved and the number of rectal procedures performed by non-colorectal surgeons decreased., Conclusions: The ability of audit to change practice has been demonstrated. We feel that completion of this audit cycle has improved the quality of service we provide for colorectal cancer patients in our hospital.

Aim: This pilot study utilised the sustained intraperitoneal (i.p.) dwell properties of an iso-osmotic solution of 4% icodextrin to investigate the tolerability, toxicity and feasibility of home-based i.p. 5FU adjuvant chemotherapy following resective surgery for colorectal cancer., Methods: Twenty eligible patients (Dukes' stage B and C with potentially curative resection) underwent perioperative Tenckhoff catheter placement. Ten (6 male, 4 female, aged 46-85; mean 67.5 years) received 5FU chemotherapy. After initial flushing and gradual increase in volumes of 4% icodextrin alone, patients received home-based i.p. 5FU (150-300 mg/m(2)/day given as equal doses at 12-hourly intervals) for 14 days, with a 14-day recovery period, for a maximum of 6 courses. Two incurable patients, treated on compassionate grounds, provided further safety data., Results: Nine of the 10 patients became proficient in self-treatment with 5FU and two completed 6 courses. Frequent abdominal pain was the main dose-limiting toxicity of 5FU, causing withdrawal of three patients after a high (300 mg/m(2)/day) first course and one following a third course at lower doses. I.p. 5FU concentrations (mean>30000 ngml(-1)) were 1000 fold higher than systemic venous levels. Bacterial peritonitis led to two withdrawals but was not a frequent event (microbiologically confirmed incidence of 1 per 27 catheter-months)., Conclusions: Home-based i.p. adjuvant chemotherapy is a feasible treatment option in patients with surgically resected colorectal carcinoma.

Background: The perianal region is a very rare location for Hodgkin's lymphoma, and clinicians may often neglect the diagnosis in patients with inflammatory bowel disease., Patient Presentation: We present a case of perianal Hodgkin's lymphoma in patient with Crohn's disease who was on long-term immunosuppression and whose symptoms would normally be attributed to Crohn's disease. Diagnosis was based on the morphological appearance of atypical cells in the lamina propria and the immunohistochemical profile of Reed Sternberg and Hodgkin's cells, showing co-expression of CD15 and CD30., Conclusion: Perianal complaints in patients with inflammatory bowel disease may be a manifestation of other pathology. Hodgkin's lymphoma could be a progression in the chronically inflamed tissue in this unusual location.

Aims: Blood transfusions are often given to surgical patients. This study was designed to assess whether acute normovolaemic haemodilution (ANH) reduces exposure to allogeneic blood, affects clinical outcome and hospital stay, and is feasible in colorectal surgery., Methods: All ASA 1 and 11 patients undergoing colectomies performed between 1997 and 1999 were identified retrospectively from our colorectal cancer database to ascertain our current peri and postoperative transfusion practice. Twenty-six selected patients subsequently underwent ANH during colectomy surgery. The number of patients and units transfused were identified., Results: One hundred and twenty-three of 317 (39%) patients identified from our colorectal cancer database were transfused a total of 328 units (median 2, range 1-7). Of the 26 patients undergoing ANH, 4 (15%) were transfused a total of 13 units (median 3, range 2-5). The reduction in number of patients transfused was statistically significant (P=0.017). ANH increased anaesthetic time by a median of 19 min. There were no complications associated with ANH and the median hospital stay was 9 days (range 6-13)., Conclusions: In this pilot study of selected patients, ANH is a feasible and effective method of reducing allogeneic blood exposure in major colorectal surgery. A prospective randomised controlled trial is now urgently required.

Background: Bowel preparation using purgatives has previously been shown significantly to increase haemoglobin concentration and decrease weight. This prospective randomized study assessed the effects of administering intravenous fluid during bowel preparation., Methods: Patients having bowel preparation with Picolax for colonic procedures were randomized prospectively to receive no intravenous fluid (group 1) or calculated intravenous crystalloid based on body-weight (group 2) during preparation. Physiological, haematological and biochemical variables were measured before and after bowel preparation., Results: Forty-one patients were recruited with a median age of 69 (range 29-86) years, 22 in group 1 and 19 in group 2. There was no difference between groups in any of the variables measured before bowel preparation. On completion, there was a significant difference between groups in mean weight loss (P = 0.01), postural change in systolic pressure (P = 0.015) and serum creatinine concentration (P = 0.008). In addition there was a significant fall in erect blood pressure after bowel preparation in group 1 (P = 0.02). The mean urine output in group 1 was 982 ml and in group 2 was 1808 ml (P = 0.004). The faeces weight between groups was not significantly different., Conclusion: Picolax bowel preparation has a significant dehydrating effect, which can be minimized by administering a simultaneous volume of intravenous fluid (mean 2 litres in this study).

Aim: To evaluate whether the assessment of multiple sections from retrieved nodes yields an increased number of metastases compared with the number that would be detected by the commonly applied method of microscopy of a single section of lymph node only., Methods: A prospective study of 72 colorectal carcinoma resection specimens. Lymph node sampling was based on the current guidelines for the detection of breast cancer metastases in axillary nodes. Lymph nodes up to approximately 5 mm in maximum extent were processed in entirety, without prior sectioning, and assessed histologically at three levels; larger lymph nodes were processed in entirety as multiple sections and histologically assessed at one level., Results: From a total of 72 carcinomas, eight were Dukes's A, 26 were Dukes's B, and 38 were Dukes's C. The mean and median numbers of nodes identified were 13 and 12, respectively (range, three to 44). Of the Dukes's C cases, four contained lymph node metastases identified by our method that might have gone undetected by the current, generally applied method. In one case, this led to the detection of the only nodal metastasis present and therefore "upstaged" the tumour from Dukes's B to C. On average, six extra tissue blocks were processed for each case in applying this method., Conclusion: The assessment of multiple sections of lymph nodes from colorectal specimens leads to the detection of only a small number of additional nodal metastases. The method involves increased workload for pathologists and laboratory staff.

Background: The value of introducing a short course of preoperative radiotherapy before operation for rectal cancer is still subject to debate., Methods: One hundred consecutive patients, of mean age 68 (range 29-87) years undergoing pre- operative radiotherapy for rectal cancer between January 1997 and December 1998 at two radiotherapy centres were audited prospectively., Results: The time from referral to radiotherapy was 33 (11-74) days and from radiotherapy to operation 5 (1-42) days. There was a higher than expected anastomotic leak rate (15 per cent) and perineal wound infection rate (18 per cent). Patients waiting more than 7 days were more likely to suffer perineal wound breakdown: 15 per cent (n = 39) versus 30 per cent (n = 10)., Conclusion: The high anastomotic leak and perineal wound infection rates suggest that the introduction of preoperative radiotherapy combined with total mesorectal excision should be audited carefully or performed as part of the CRO7 trial. Presented to the Association of Coloproctology of Great Britain and Ireland in St Helier, Jersey, June 1998

We report a case of squamous cell carcinoma of the colon in an asbestos worker. We speculate whether the asbestos exposure could have been causative and review the literature., (Copyright 1999 Harcourt Publishers Ltd.)

The detail and accuracy of pathological reporting for colorectal cancer is becoming increasingly recognised as important in the overall management of the patient. However, there is criticism of the variable standards of reporting. We assessed how the use of a proforma affected the completeness of reporting within one hospital. Data on all colorectal cancer patients attending one teaching hospital has been collected prospectively over a 15 month period from 1997 to 1998. The Royal College of Surgeons/Association of Coloproctology proforma lists all items considered to be essential for a complete pathological report of colorectal cancer. Its introduction in September 1997 allowed us to compare reporting before the proforma to that after. Of 54 patients, 46 (85%) had one or more items missing from their report before introduction of the proforma compared with only 8/44 (18%) patients after the proforma (P < 0.001). Circumferential resection margins and apical node status were the items most often absent, being significantly more frequently reported after the proforma (P < 0.05 and P < 0.001, respectively). There was no difference in the median number of lymph nodes harvested after proforma introduction. The introduction of the proforma has not only resulted in improvements in reporting, but has increased the dialogue between surgical oncologists and pathologists. These features should result in improved overall management of the colorectal cancer patient.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Background: High-grade anal intraepithelial neoplasia (Bowen's disease) may predispose to anal carcinoma. Treatment options include surgical resection but effectiveness remains uncertain. This paper reports long-term follow-up of patients with high-grade anal intraepithelial neoplasia treated by surgical resection., Methods: Between 1989 and 1996, 46 patients were identified with high-grade anal intraepithelial neoplasia. Thirty-four underwent local excision of all macroscopically abnormal disease and the resulting defect was left open, closed primarily or skin grafted. Regular follow-up subsequently included anoscopy and biopsy of any suspicious lesions., Results: Median follow-up was 41 (range 12-104) months. Total excision was difficult; 19 patients had histological evidence of incomplete excision at the time of initial resection. Some 12 of 19 had histo-logically proven recurrent high-grade intraepithelial neoplasia within 1 year. Even with microscopically complete excision two of 15 patients subsequently developed recurrent high-grade intraepithelial neoplasia at 6 and 32 months after operation. No patient developed carcinoma but five had complica-tions of anal stenosis or faecal incontinence., Conclusion: Although no definite recommendations can be made for the treatment of high-grade anal intraepithelial neoplasia, these results illustrate some potential drawbacks of surgical excision with a high potential for incomplete excision and persistent disease, even after complete excision in some patients, and a high morbidity rate.

A case of gangrenous cystitis presenting as a colovesical fistula in an elderly woman is described. The literature on this rare condition is reviewed.

1. Oligonucleotide primers based on the human heart monocarboxylate transporter (MCT1) cDNA sequence were used to isolate a 544 bp cDNA product from human colonic RNA by reverse transcription-polymerase chain reaction (RT-PCR). The sequence of the RT-PCR product was identical to that of human heart MCT1. Northern blot analysis using the RT-PCR product indicated the presence of a single transcript of 3.3 kb in mRNA isolated from both human and pig colonic tissues. Western blot analysis using an antibody to human MCT1 identified a specific protein with an apparent molecular mass of 40 kDa in purified and well-characterized human and pig colonic lumenal membrane vesicles (LMV). 2. Properties of the colonic lumenal membrane L-lactate transporter were studied by the uptake of L-[U-14C]lactate into human and pig colonic LMV. L-Lactate uptake was stimulated in the presence of an outward-directed anion gradient at an extravesicular pH of 5.5. Transport of L-lactate into anion-loaded colonic LMV appeared to be via a proton-activated, anion exchange mechanism. 3. L-Lactate uptake was inhibited by pyruvate, butyrate, propionate and acetate, but not by Cl- and SO4(2-). The uptake of L-lactate was inhibited by phloretin, mercurials and alpha-cyano-4-hydroxycinnamic acid (4-CHC), but not by the stilbene anion exchange inhibitors, 4,4'-diisothiocyanostilbene-2, 2'-disulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2, 2'-disulphonic acid (SITS). 4. The results indicate the presence of a MCT1 protein on the lumenal membrane of the colon that is involved in the transport of L-lactate as well as butyrate across the colonic lumenal membrane. Western blot analysis showed that the abundance of this protein decreases in lumenal membrane fractions isolated from colonic carcinomas compared with that detected in the normal healthy colonic tissue.

1. Luminal membrane vesicles (LMV) were isolated from human and pig colonic tissues. They were characterized in terms of purity and ability to transport [14C]butyrate. 2. The activity of cysteine-sensitive alkaline phosphatase, and the abundance of villin, NHE2 and NHE3 proteins, markers of the colonic luminal membrane, were significantly enriched in the LMV compared with the original cellular homogenate. The LMV were free from contamination by other cellular organelles and basolateral membranes, as revealed by the negligible presence of either specific marker enzyme activity or characteristic immunogenic protein. 3. The transport of butyrate into the luminal membrane vesicles was enhanced 5-fold at pH 5.5 compared with pH 8.0. Butyrate transport was temperature dependent, and was stimulated in the presence of an outward-directed anion gradient in the order of butyrate > bicarbonate > propionate > chloride. Kinetic analysis of increasing substrate concentration showed saturation kinetics with an apparent Km value of 14.8 +/- 3.6 mM and a Vmax of 54 +/- 14 nmol min-1 (mg protein)-1. 4. Butyrate transport was significantly reduced in the presence of short chain fatty acids (SCFA), acetate, propionate and other monocarboxylates (pyruvate and L-lactate). Butyrate uptake was inhibited by several cysteine group modifying reagents such as p-chloromercuribenzosulphonic acid (pCMBS), p-chloromercuribenzoate (pCMB), mersalyl acid and HgCl2, but not by the stilbene anion exchange inhibitors, 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS) and 4,4'-dinitrostilbene-2,2'-disulphonate (SITS). 5. The described properties of butyrate transport across the luminal pole of the colon suggest the involvement of a carrier protein, in the form of a pH-activated anion exchange process. The transporter is distinct from the erythrocyte band-3 type anion exchanger and may belong to the monocarboxylate-type transport proteins (MCT1).

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.

Background: The activity of most intestinal nutrient transporters is adaptively regulated by the type and amounts of nutrients entering the intestinal lumen. The concentration and activity of the intestinal Na+/glucose cotransporter (SGLT1) are regulated by dietary sugars in most animal species. The activity and abundance of SGLT1 in biopsy specimens removed from human jejunal regions exposed to, and having limited access to, luminal nutrients have been measured and compared., Aims: To study the effects of luminal nutrients on the expression of SGLT1 in the human intestine., Patient and Methods: Brush border membrane vesicles (BBMV) were prepared from biopsy specimens removed from the intestine of a 50 year old man who had developed a high output jejunal fistula, and adjacent mucosal fistula, a condition present for 12 months after surgery for a strangulated hernia. BBMV prepared from intestine exposed to luminal nutrients, and from dysfunctional intestine with a limited exposure to nutrients, were used to measure Na+ dependent glucose transport and abundance of SGLT1 protein., Results: The levels of SGLT1 activity and abundance in the BBMV prepared from control biopsy specimens were similar to those found in BBMV prepared from the intestine of healthy individuals. BBMV from the dysfunctional intestine, exposed to limited levels of luminal nutrients, had reduced levels of SGLT1 activity. This reduction in SGLT1 activity and abundance was above that associated with any villus atrophy, as assessed by the abundance/activity of lactase and villin concentrations., Conclusions: These data indicate that the activity and expression of SGLT1 in human intestine is maintained by the presence of luminal nutrients.

Radical resection of gastric cancer offers the best hope of cure, but carries the risk of significant psychological morbidity in addition to the well-documented physical complications. In the case presented, recognition of clinical depression after thoracoabdominal gastrectomy enabled successful psychological intervention.

The effects of antireflux surgery on Barrett's oesophagus were studied. Fifty-six patients (45 men and 11 women of median age 48.5 (range 20-78) years) with histologically confirmed Barrett's oesophagus (greater than 3 cm in length) and gastro-oesophageal reflux underwent antireflux surgery. Symptoms were noted and patients underwent manometry and pH recording before and after operation, and annual flexible endoscopy. Fundoplication resulted in a significant improvement in lower oesophageal sphincter pressure (median (interquartile range (i.q.r.)) 8 (5-14) mmHg before operation versus 17 (11-22) mmHg after operation, P < 0.001). Twenty-four of the 56 patients had partial or complete regression of Barrett's oesophagus (median (i.q.r.) length 8 (3-18) cm before versus 4 (0-10) cm after operation, P < 0.001) but nine showed progression (median (i.q.r.) length 6 (3-11) cm before versus 10 (6-15) cm after operation, P < 0.01) (median follow-up 5.5 (range 2.0-10.5) years). Carcinoma developed in one patient. The length of Barrett's oesophagus was unchanged in 23 patients. Regression was more likely to occur in patients who underwent fundoplication with previous or concomitant vagotomy (chi 2 = 7.21, 1 d.f., P < 0.01) and in those with a good symptomatic result (chi 2 = 23.52, 1 d.f., P < 0.001).

Between 1979 and 1984, 141 patients (110 men, 31 women) underwent highly selective vagotomy (HSV) by a standard open technique for duodenal ulcer. All patients had received preoperative treatment with full-dose H2-receptor antagonists. Some 107 of these patients underwent HSV for persistent relapse on withdrawal of H2-receptor antagonists (relapsing responders) and 30 because of non-response to such drugs. After 4 years of follow-up, non-responders were found to be more likely to have symptoms after operation (P < 0.001), but did not have a higher rate of recurrent ulceration. At a median of 11 (range 8-14) years after operation 126 patients were still alive; 115 (91 per cent) of these were followed up. Ten patients (9 per cent) were found to have had endoscopically proven recurrence and eight (7 per cent) still had symptoms without evidence of recurrence. The endoscopic recurrence rate and symptom rate at 11 years were no longer significantly different between relapsing responders and non-responders. The preoperative response to H2-receptor antagonist therapy does not help in predicting the likelihood of ulcer recurrence or long-term symptoms after HSV. Post-operative symptoms do not necessarily predict long-term ulcer recurrence. The long-term endoscopic recurrence rate after HSV is low and, if equally good results can be obtained laparoscopically, this will be an important and cost-effective option in the management of duodenal ulcer.

Complex sclerosing lesion (CSL)/radial scar and carcinoma of breast can both present mammographically as stellate lesions. The mammographic features used to distinguish these two entities are reported as being unreliable. All reports to date indicate that CSLs are not palpable. Of the 54,407 women screened in the first 2 1/2 years of the Warwickshire, Solihull and Coventry Breast Screening Service, 24 histologically-proven CSLs were identified. This represents an incidence of 0.04%. In six (25%) of these patients a corresponding clinically-palpable abnormality was identified. We found no imaging or histological features that differentiated the palpable lesions from the impalpable lesions. It is important not to assume that a palpable stellate lesion is a carcinoma.

Twenty of 81 patients treated by restorative proctocolectomy for presumed ulcerative colitis had some features of Crohn's disease: 10 were classified as definite Crohn's disease and 10 as indeterminate colitis. These pathological features were first apparent during synchronous colectomy and pouch construction in 10 of 11 cases. In the remainder, histological features of possible Crohn's disease were first identified during rectal excision (n = 6), preliminary subtotal colectomy (n = 2), and after pouch excision (= 2). Complications were marginally more common in patients with features of possible Crohn's disease: pelvic sepsis 30% (Crohn's disease 30%, indeterminate colitis 30%) v 20%, fistulas 45% (Crohn's disease 30%, indeterminate colitis 60%) v 16%; ileal stenosis 40% (Crohn's disease 40%, indeterminate colitis 40%) v 21%, pouchitis 50% (Crohn's disease 50%, indeterminate colitis 50%) v 26%, and small bowel obstruction 25% (Crohn's disease 30%, indeterminate colitis 30%) v 13%. Pouch excision or a persistent proximal stoma has been necessary in six patients with possible Crohn's disease (30%) (Crohn's disease 3 cases 30%, indeterminate colitis 3 cases 30%) compared with nine (15%) of the remainder. Median hospital stay, however, was the same and stool frequency in those with a functioning pouch were comparable. These results show that there is a higher complication rate if there are features of Crohn's disease but that the medium term functional results are acceptable if the pouch can be retained.