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.

Inhibitory and anti-inflammatory effects of the Helicobacter pylori-derived antimicrobial peptide HPA3NT3 against Propionibacterium acnes in the skin.

BACKGROUND: An effective treatment strategy for acne vulgaris is the reduction of Propionibacterium acnes in the skin. The Helicobacter pylori-derived synthetic antimicrobial peptide HPA3NT3 is a customized α-helical cationic peptide with antibacterial and anti-inflammatory activity. OBJECTIVES: To examine the role of HPA3NT3 as a treatment against P. acnes-induced skin inflammation. METHODS: Morphological alteration of individual P. acnes cells by HPA3NT3 was visualized by scanning electron microscopy. Modulation by HPA3NT3 of a number of P. acnes-induced innate immune responses was analysed in vitro using cultured normal human keratinocytes (HKs), and in vivo using the ICR mouse, a well-established model for P. acnes-induced skin inflammation. RESULTS: The minimum inhibitory concentration of HPA3NT3 against P. acnes was low (0·4 µmol L(-1)). HPA3NT3 showed no cytotoxicity to HK cells at the concentrations used in our in vitro and in vivo studies. Treatment with HPA3NT3 in vitro induced morphological disruptions in P. acnes cells suggestive of a bactericidal effect. HPA3NT3 significantly decreased P. acnes-induced interleukin-8 expression and intracellular calcium mobilization in HK cells by inhibiting P. acnes-activated Toll-like receptor 2-mediated nuclear factor-κB signalling pathways. Intradermal injection of HPA3NT3 in vivo effectively decreased viable P. acnes, as well as erythema, swelling and inflammatory-cell infiltration in ICR mouse ears inoculated with P. acnes. CONCLUSIONS: Our data suggest that HPA3NT3 has potential as a therapeutic agent for acne vulgaris due to its antimicrobial effects on P. acnes and its ability to block P. acnes-induced inflammation.

Should laparoscopic reversal of Hartmann's procedure be the first line approach in all patients?

BACKGROUND/AIMS: To assess if the laparoscopic reversal of Hartmann's can be attempted in all patients, without detriment to short or long-term outcomes if the patient is subsequently converted to open. METHODS: Retrospective review of a prospectively collected database of all reversals under 8 surgeons at a single unit over 105 months, two surgeons attempting laparoscopic reversal in all patients, two pre-selecting for the laparoscopic approach and four utilising the open approach. Long-term follow-up data for re-admissions, re-operations and incisional hernia rate obtained from a postal questionnaire. RESULTS: 45 laparoscopic and 50 primary open reversals were identified. There was no difference in the mean age or previous peritonitis rate in either group. Laparoscopic conversion rate was 29% (13 patients). On intention to treat analysis, a significant difference was identified in the overall 30-day post-operative surgical morbidity (8.9% Laparoscopic-attempted vs 26.0% Open, p = 0.030). There was no difference in operating times (mean 164 vs 172 min, p = 0.896) despite the 13 patients converted to an open procedure. Mean length of stay was significantly lower in the laparoscopic-attempted group at 6.8 days (5.2-8.4) vs 14.9 days (6.4-23.7) in the open group (p = 0.001). Anastomotic leak rates were not statistically different. The median follow up was 27 months (range 6-105); 60% of patients completed a postal follow-up questionnaire. There was no difference in short-term or long-term re-admission or reoperation rates. CONCLUSIONS: Laparoscopic reversal of Hartamann's is associated with shorter hospital stay and lower morbidity even in unselected patients. Long-term outcomes are similar.

Financial impact of surgical training on hospital economics: an income analysis of 1184 out-patient clinic consultations.

INTRODUCTION: In many countries healthcare commissioning bodies (state or insurance-based) reimburse hospitals for their activity. The costs associated with post-graduate clinical training as part of this are poorly understood. This study quantified the financial revenue generated by surgical trainees in the out-patient clinic setting. METHODS: A retrospective analysis of surgical out-patient ambulatory care appointments under 6 full-time equivalent Consultants (Attendings) in one hospital over 2 months. Clinic attendance lists were generated from the Patient Access System. Appointments were categorised as: 'new', 'review' or 'procedure' as per the Department of Health Payment by Results (PbR) Outpatient Tariff (Outpatient Treatment Function Code 104; Outpatient Procedure Code OPRSI1). RESULTS: During the study period 78 clinics offered 1184 appointments; 133 of these were not attended (11.2%). Of those attended 1029 had sufficient detail for analysis (98%). 261 (25.4%) patients were seen by a trainee. Applying PbR reimbursement criteria to these gave a projected annual income of £GBP 218,712 (€EU 266,527; $USD 353,657) generated by 6 surgical trainees (Residents). This is equivalent to approximately £GBP 36,452 (€EU 44,415; $USD 58,943) per trainee annually compared to £GBP 48,732 (€EU 59,378; $USD 78,800) per Consultant. This projected yearly income off-set 95% of the trainee's basic salary. CONCLUSION: Surgical trainees generated a quarter of the out-patient clinic activity related income in this study, with each trainee producing three-quarters of that generated by a Consultant. This offers considerable commercial value to hospitals. Although this must offset productivity differences and overall running costs, training bodies should ensure hospitals offer an appropriate return. In a competitive market hospitals could be invited to compete for trainees, with preference given to those providing excellence in training.

Leaving a mark: the frequency and accuracy of tattooing prior to laparoscopic colorectal surgery.

AIM: Intra-operative localization of small cancers and polyps during laparoscopic colorectal surgery is difficult due to reduced tactile feedback. The consequences of failing to identify the lesion for resection can result in open conversion or removal of the wrong segment of bowel. METHOD: Data were collected from a prospectively-kept database over a 12-month period from April 2008 to March 2009 and analysed retrospectively. Details concerning the documentation, visibility and accuracy of tattoos were recorded. RESULTS: Eighty-five patients (88 lesions) underwent laparoscopic resection for a benign or malignant colorectal tumour during 1 year from April 2008. Eighty-one patients underwent endoscopic visualization of the tumour as a first or second procedure. Of these 81 patients, 83 lesions were visualized endoscopically and 54 (65.1%) were tattooed in 52 patients. In the 52 patients, 36 (69%) of the tattoos were carried out on the first endoscopy. At operation the tattoo was judged to be visible and accurate in 70%, visible but inaccurate in 7% and not visible in 15%. It was significantly easier to see the tattoo in women (19/21 women vs 21/29 men; P=0.03) but there was no relationship between tattoo visibility and BMI. An accurate tattoo did not reduce the conversion rate (P=0.71). No tattoo-related complications were encountered. CONCLUSION: The practice of tattooing colorectal cancers is variable in frequency, technique and accuracy. We advocate that all colonic lesions suspicious for cancer should be tattooed during endoscopy at a defined distance below the tumour, adhering to a departmental protocol in case surgery is required.

From small acorns--developing a laparoscopic colorectal surgical service.

INTRODUCTION: Randomised controlled trials have shown that laparoscopic colorectal surgery is equal in terms of safety to open surgery. Benefits have been seen for length of stay, blood loss, immune suppression and analgesia requirements. The aim of this study was to assess the safety and feasibility of introducing laparoscopic colorectal surgery to our unit. PATIENTS AND METHODS: Prospectively collected cases of all patients undergoing laparoscopic colorectal surgery between July 2003 and July 2007 were reviewed. RESULTS: A total of 143 patients (75 males and 68 females) with a mean age of 65.8 years (range, 21-95 years) underwent surgery. Laparoscopic resection for colorectal malignancy was performed in 93 patients (65%). The conversion rate for all cases was 14.7%. Mean operative time was 203 min (range, 100-400 min), with a mean blood loss of 180 ml. The mean number of lymph nodes in malignant cases was 13.8 with clear resection margin in all but one case. The mean postoperative stay was 5.6 days (median, 4 days; range, 2-35 days). UKCCR standard for lymph node retrieval was achieved in 62.6% of cases. There were four postoperative deaths. The overall 30-day morbidity rate was 21.7%. The service is consultant-led with 9.8% of cases performed by senior trainees and 37% of procedures performed by two consultants. CONCLUSIONS: Laparoscopic colorectal surgery is technically feasible and safe in our hands. Although operative time is longer, this is counterbalanced by shorter hospital stay. The results from this series support the findings of others and continuing development of this service.

Are we teaching sufficient anatomy at medical school? The opinions of newly qualified doctors.

In recent decades wide-ranging changes have occurred in medical school curricula. Time spent studying gross anatomy has declined amidst controversy as to how, what, and when teaching is best delivered. This reduced emphasis has led to concerns amongst clinicians that a new generation of doctors are leaving medical school with insufficient anatomical knowledge. Previous studies have established that medical students value their anatomy teaching during medical school. None have sought to establish views on the sufficiency of this teaching. We investigate the opinions of newly qualified doctors at a UK medical school and relate these opinions to career intentions and academic performance in the setting of a traditional dissection and prosection-based course. Overall nearly half of respondents believe they received insufficient anatomy teaching. A substantial proportion called for the integration of anatomy teaching throughout the medical school course. Trainees intent on pursuing a surgical career were more likely to believe anatomy teaching was insufficient than those pursuing a nonsurgical career; however, overall there was no statistical difference in relation to the mean for any individual career group. This study adds to the current debates in anatomical sciences education, indicating that overall, regardless of career intentions, new doctors perceive the need for greater emphasis on anatomical teaching.

A prospective audit of early pain and patient satisfaction following out-patient band ligation of haemorrhoids.

INTRODUCTION: Information regarding early morbidity, pain and patient satisfaction following band ligation of haemorrhoids is limited. This is the first report to address these issues specifically. PATIENTS AND METHODS: A total of 183 patients underwent the procedure over a 10-month period. Prospective data were collected using a detailed structured questionnaire regarding symptoms, analgesia requirements and patient satisfaction in the following week. RESULTS: The response rate was 74% (135/183). Pain scores were highest 4 h following the procedure. At 1 week, 75% of patients were pain-free, with 9 (7%) still experiencing moderate-to-severe pain. About 65% required oral analgesia, most frequently on the day of procedure. Rectal bleeding occurred in 86 patients (65%) on the day after banding, persisting in 32 (24%) at 1 week. Vaso-vagal symptoms occurred in 41 patients (30%) and were commonest at the time of banding. Eighty patients (59%) were satisfied with their experience and would undergo the procedure again. Patients requiring oral analgesia and those experiencing bleeding or vaso-vagal symptoms were significantly less likely to be satisfied with the procedure. Only 57% of the patients surveyed would recommend the procedure to a friend. CONCLUSIONS: Data from this large cohort of patients suggest that discomfort and bleeding may persist for a week or more following banding of haemorrhoids. Patients should be aware of this in order to make an informed decision as to whether to undergo the procedure, and surgeons should investigate ways of reducing it. Patient satisfaction may be further improved by more accurate counselling regarding the incidence of specific complications.

Low-intensity hematopoietic stem-cell transplantation across human leucocyte antigen barriers in dyskeratosis congenita.

Since the results of conventional hematopoietic stem-cell transplantation (HSCT) for patients with dyskeratosis congenita (DC) are poor owing to the high incidence of transplant-related complications, we explored the use of a low-intensity HSCT regimen. We report two children with DC with severe cytopenia, who underwent successful HSCT from a matched unrelated donor after conditioning with fludarabine, cyclophosphamide, and antithymocyte globulin. Graft-versus-host-disease (GVHD) prophylaxis consisted of corticosteroids and cyclosporin A. The regimen was well tolerated, no significant transplant-related complications were observed, and engraftment was rapid and complete. At 15 and 16 months after HSCT, the children were fully engrafted, in excellent clinical condition, full-donor chimerism, and no signs of GVHD. We conclude that a low-intensity regimen is sufficient to induce durable engraftment using matched unrelated donor HSCT in DC patients, with minimal 1-year transplant-related toxicity. Longer follow-up will determine whether this regimen also reduces long-term toxicity.

Alpha-melanocyte stimulating hormone prevents lipopolysaccharide-induced vasculitis by down-regulating endothelial cell adhesion molecule expression.

The neuroendocrine hormone alpha-melanocyte stimulating hormone (MSH) has profound antiinflammatory and immunomodulating properties. Here we have examined the possibility that alpha-MSH may interfere with the expression and function of cell adhesion molecules (CAMs) expressed by human dermal microvascular endothelial cells (HDMECs) in response to lipopolysaccharide (LPS) or TNFalpha in vitro and in vivo. In HDMEC, alpha-MSH (10(-8)/10(-12) M) profoundly reduced the mRNA and protein expression of E-selectin, vascular CAM (VCAM)-1, and intercellular CAM (ICAM)-1 induced by LPS or TNFalpha as determined by semiquantitative RT-PCR, ELISA, and fluorescence-activated cell sorter analysis. In addition, alpha-MSH significantly impaired the LPS-induced ICAM-1 and VCAM-1-mediated adhesion of lymphocytes to HDMEC monolayer in a functional adhesion assay. Likewise, alpha-MSH effectively inhibited the transcription factor nuclear factor-kappaB activation in HDMEC, which is required for CAM gene expression. Importantly in vivo, in murine LPS-induced cutaneous vasculitis (local Shwartzman reaction), a single ip injection of alpha-MSH significantly suppressed the deleterious vascular damage and hemorrhage by inhibiting the sustained expression of vascular E-selectin and VCAM-1. This persistent expression has been implicated in the dysregulation of diapedesis and activation of leukocytes, which subsequently leads to hemorrhagic vascular damage. Our findings indicate that alpha-MSH may have an important therapeutical potential for the treatment of vasculitis, sepsis, and inflammatory diseases.

Current concepts in immunotherapy for the treatment of colorectal cancer.

Immunotherapy could have a role in the therapy of colorectal cancer as there is now convincing evidence that the immune system can specifically recognize and destroy malignant cells. The MAb 17-1A has been used in advanced and primary disease, along with newer agents such as anti-epidermal growth factor receptor (EGFR) antibody. Immunotherapy with autologous tumour cell vaccine, genetic modification of immunostimulatory cytokines, suicide genes and TAAs as discussed. The multiplicity of peptide and carbohydrate antigens which can be potential targets for immunotherapy are also discussed. These include MUC1, Thomsen-Friedenreich and Sialosyl-Tn antigens and HER2 / neu. Active specific immunotherapy with the anti-idiotypic antibodies CEAVac and 105AD7, along with DC vaccines, is being currently used in adjuvant clinical trials. 105AD7 has been shown to cause significantly greater apoptosis of tumour cells in colorectal cancer patients, while CEAVac generated T cell proliferative anti-CEA responses. Dendritic cells pulsed with tumour mRNA or TAAs currently are being assessed in clinical trials. The role of HSPs in the anti-tumour immune response is discussed. Non-specific immunotherapeutic agents used in clinical trials with chemotherapeutic regimens have not shown any definitive benefit. Tumour progression may occur as result of escape from the host anti-cancer immune response. Better understanding of mechanisms of tumour evasion could explain why immunotherapy trials in patients have not shown better results. These include down-regulation of immune responses by the tumour, altered expression of MHC and/or TAAs by tumour cells, altered expression of adhesion molecules by tumour and/or DCs and usurpation of the immune response to the advantage of the cancer.

The expression of functional LPS receptor proteins CD14 and toll-like receptor 4 in human corneal cells.

PURPOSE: Gram-negative bacterial infections of the eye can lead to corneal bacterial keratitis, visual impairment, and blindness. Many of these pathologic changes may be mediated by bacterially derived products such as lipopolysaccharide (LPS). In this investigation, it has been established for the first time that human corneal cells are capable of expressing the functional LPS receptor complex proteins, CD14 and Toll-like receptor 4 (TLR4). METHODS: CD14 and TLR4 mRNA expression in human corneal cells was determined by RT-PCR and Northern blot analysis, and cell surface expression of these proteins was measured by flow cytometry. LPS-mediated corneal cell activation was determined by measuring intracellular calcium mobilization. Cellular cytokine and chemokine secretion in response to LPS was measured by ELISA. The expression and localization of CD14 in whole human cornea was determined by immunohistochemistry. RESULTS: Human corneal epithelial, stromal, and endothelial cells expressed CD14 mRNA and cell surface CD14. LPS binding to cornea CD14 resulted in a rapid intracellular calcium response and the secretion of multiple proinflammatory cytokines and chemokines. CD14 mRNA expression in corneal epithelial cells was upregulated by LPS. In addition to CD14, corneal epithelial cells expressed the functional LPS receptor-signaling protein TLR4, which was also augmented by LPS. CONCLUSIONS: The cornea expresses functional CD14 and TLR4 LPS receptor proteins. Understanding the function and biology of the corneal LPS receptor complex may lead to novel therapies for the management of ocular Gram-negative bacterial infections.

Management of high-risk melanoma.

Improved treatment options for patients with high-risk melanoma are of great importance for clinicians who participate in the care of these patients. There remains an overall lack of response to existing treatment options, which continues to fuel the efforts of basic scientists and clinicians to pursue other approaches for the treatment of melanoma that is no longer limited to the skin. Continued investigation into the innovative and concurrent use of surgery, chemotherapy, immunotherapy, and radiation therapy holds significant promise for improved outcomes in the management of patients with this devastating disease.