Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project.

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons.

The vitamin D receptor Taq I polymorphism is associated with reduced VDR and increased PDIA3 protein levels in human intestinal fibroblasts.

The synonymous single nucleotide polymorphism (SNP) rs731236, located in the vitamin D receptor (VDR) gene (Taq I) has been associated with both decreased levels of the protein in peripheral blood mononuclear cells and a fibrosis-related complication in Crohn´s disease (CD). Interactions between VDR and a protein-disulfide isomerase-associated 3 (PDIA3) in the regulation of extracellular matrix have been reported and we aim to analyze the relevance of the VDR genotypes and the effects of Vitamin D (VD) in the expression of VDR, PDIA3 and proliferation of intestinal fibroblasts. Human intestinal fibroblasts were isolated from the non-affected surgical resections of colorectal patients and classified according to the VDR genotype.

Succinate Activates EMT in Intestinal Epithelial Cells through SUCNR1: A Novel Protagonist in Fistula Development.

The pathogenesis of Crohn's disease-associated fibrostenosis and fistulas imply the epithelial-to-mesenchymal transition (EMT) process. As succinate and its receptor (SUCNR1) are involved in intestinal inflammation and fibrosis, we investigated their relevance in EMT and Crohn's disease (CD) fistulas. Succinate levels and SUCNR1-expression were analyzed in intestinal resections from non-Inflammatory Bowel Disease (non-IBD) subjects and CD patients with stenosing-B2 or penetrating-B3 complications and in a murine heterotopic-transplant model of intestinal fibrosis.

Recommendations of the Crohn's Disease and Ulcerative Colitis Spanish Working Group (GETECCU) for the treatment of perianal fistulas of Crohn's disease.

Recommendations are advice that is given and considered to be beneficial; however, they are still suggestions and are therefore open to different interpretations. In this sense, the final objective of the review has been to try to homogenize, with the evidence available, the approach to the diagnosis and medical/surgical treatment of one of the most complex manifestations of Crohn's disease, such as simple and complex perianal fistulas.

Autophagy Stimulation as a Potential Strategy Against Intestinal Fibrosis.

We recently observed reduced autophagy in Crohn's disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn's disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts.

WNT2b Activates Epithelial-mesenchymal Transition Through FZD4: Relevance in Penetrating Crohn´s Disease.

Background And Aims: Epithelial-mesenchymal transition [EMT] has been related to fibrosis and fistula formation, common complications associated with Crohn´s disease [CD]. The WNT signalling pathway mediates EMT, and specific WNT/FZD interactions have been related to the activation of this process in several diseases. We aim to analyse the relevance of EMT and WNT ligands and receptors in the penetrating behaviour of CD.

Succinate receptor mediates intestinal inflammation and fibrosis.

Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation and fibrosis. We show that both serum and intestinal succinate levels and SUCNR1 expression in intestinal surgical resections were higher in CD patients than in controls.

CD16+ Macrophages Mediate Fibrosis in Inflammatory Bowel Disease.

Background And Aims: Fibrosis is a common complication of Crohn's disease [CD], and is related to dysregulated tissular repair following inflammation, in which macrophages play a central role. We have previously observed that STAT6-/- mice present delayed mucosal recovery after 2,4,6-trinitrobenzenesulfonic acid [TNBS]-induced colitis due to a deficiency in reparatory interleukin-4 [IL4]/STAT6-dependent M2 macrophages, which can be reverted by the exogenous transfer of this cell type. In the present study, we analyse the role of STAT6-dependent macrophages in intestinal fibrosis.

M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease.

Background: The Notch signalling pathway plays an essential role in mucosal regeneration, which constitutes a key goal of Crohn's disease (CD) treatment. Macrophages coordinate tissue repair and several phenotypes have been reported which differ in the expression of surface proteins, cytokines and hypoxia-inducible factors (HIFs). We analysed the role of HIFs in the expression of Notch ligands in macrophages and the relevance of this pathway in mucosal regeneration.

[Postpartum incontinence. Narrative review].

The development of fecal incontinence after childbirth is a common event. This incontinence responds to a multifactorial etiology in which the most common element is external anal sphincter injury. There are several risk factors, and it is very important to know and avoid them.

Progastrin represses the alternative activation of human macrophages and modulates their influence on colon cancer epithelial cells.

Macrophage infiltration is a negative prognostic factor for most cancers but gastrointestinal tumors seem to be an exception. The effect of macrophages on cancer progression depends on their phenotype, which may vary between M1 (pro-inflammatory, defensive) to M2 (tolerogenic, pro-tumoral). Gastrointestinal cancers often become an ectopic source of gastrins and macrophages present receptors for these peptides.

Hypoxic macrophages impair autophagy in epithelial cells through Wnt1: relevance in IBD.

A defective induction of epithelial autophagy may have a role in the pathogenesis of inflammatory bowel diseases. This process is regulated mainly by extracellular factors such as nutrients and growth factors and is highly induced by diverse situations of stress. We hypothesized that epithelial autophagy is regulated by the immune response that in turn is modulated by local hypoxia and inflammatory signals present in the inflamed mucosa.

Delphi consensus statement: Quality Indicators for Inflammatory Bowel Disease Comprehensive Care Units.

Background And Aims: While it is commonly accepted that Inflammatory bowel disease (IBD) Comprehensive Care Units (ICCUs) facilitate the delivery of quality care to Crohn's disease and ulcerative colitis patients, it remains unclear how an ICCU should be defined or evaluated. The aim of the present study was to develop a comprehensive set of Quality Indicators (QIs) of structure, process, and outcomes for defining and evaluating an ICCU.

Methods: A Delphi consensus-based approach with a standardized three-step process was used to identify a core set of QIs.

Psychosocial risk exposures and labour management practices. An exploratory approach.

Aim: The purpose was to explore the relationship between psychosocial risk exposures and labour management practices (LMP), as indicators of work organization and pertinent features for primary preventive intervention.

Methods: Cross-sectional study of a representative sample of salaried working population in Spain (n = 7,612). Information was obtained in 2004-2005 using a standardized questionnaire administered through personal interviews at the household.

Fistulectomy and sphincteric reconstruction for complex cryptoglandular fistulas.

Objective: Complex anal fistulas (CFs) are difficult to treat. Endoanal advancement flap (EAF) is one of the standard treatment options for such clinical conditions. Immediate sphincter repair after fistulectomy (ISR) is not commonly performed because of the fear of causing postoperative incontinence.

[Prevention of venous thromboembolic disease in general surgery].

Postoperative venous thromboembolic disease (VTED) affects approximately one in four general surgery patients who do not receive preventive measures. In addition to the risk of pulmonary embolism, which is often fatal, patients with VTED may develop long-term complications such as post-thrombotic syndrome or chronic pulmonary hypertension. In addition, postoperative VTED is usually asymptomatic or produces clinical manifestations that are attributed to other processes and consequently this complication is often unnoticed by the surgeon who performed the procedure.

[Risk of venous thromboembolic disease in general surgery].

Despite preventive efforts, venous thromboembolic disease (VTED) is still a major problem for surgeons due to its frequency and the morbidity, mortality and enormous resource consumption caused by this entity. However, the most important feature of VTED is that it is one of the most easily preventable complications and causes of death. To take appropriate prophylactic decisions (indication, method, initiation, duration, etc.

[Importance of physical examination and imaging techniques in the diagnosis of anorectal fistulae].

Aim: The study was designed to determine the role of clinical examination and imaging techniques in the diagnosis of anorectal fistula.

Material And Methods: We performed an observational study with prospective recruiting using the data of 120 patients, by means of clinical evaluation by an experienced coloproctologist surgeon (EE), a surgeon without special training in coloproctology (CE), and examination under anaesthesia (SE), endoanal ultrasound (EAU) and magnetic resonance (MR), using the surgical findings as a reference.

Results: SE was significantly better than EE or CE for detecting an internal opening (IO), primary track and abscess cavities (AC).

Quality of mesorectum after laparoscopic resection for rectal cancer - results of an audited teaching programme in Spain.

Objective: The aim of this prospective observational study was to compare the quality of total mesorectal excision between laparoscopic and open surgery for rectal cancer.

Method: In April 2006, the Spanish Association of Surgeons started an audited teaching programme. The project was similar to the Norwegian one and several training courses were arranged.

Timing of surgery in Crohn's disease: a key issue in the management.

The timing of the decision for operation in Crohn's disease is based on an evaluation of the several factors such as the failure of medical treatment, complications due to the Crohn's disease or to the pharmacological therapy, development of dysplasia or cancer and growth retardation. A complete evaluation of these factors should result in operation timed to the patient's best advantage, achieving maximal relief of symptoms with improvement of quality of life. Given the complexity and heterogeneity of the disease and the different options for treatment, is difficult to systematize when the optimal moment for the surgery is arrived.

Severe myalgia associated with adalimumab treatment in a patient with Crohn's disease.

Objective: To report a case of severe myalgia associated with adalimumab in a patient with Crohn's disease.

Case Summary: A 44-year-old woman was diagnosed as having ileocecal Crohn's disease with perianal fistula lesions. She was treated with 3 infusions of infliximab 5 mg/kg, which stabilized her condition.

[Audited teaching program for the treatment of rectal cancer in Spain: results of the first year].

Introduction: Rectal cancer (RC) is one of the tumors showing the greatest discrepancies in outcomes, both in terms of local recurrence (LR) and survival. In Spain, the overall LR rates are unknown, but several European studies have demonstrated that the introduction of national training programs have decreased these rates and have increased survival. The aim of the present study was to present a descriptive analysis of the first results of a national teaching program in total mesorectal excision (TME).