Eloy Espín

Increased mucosal tumour necrosis factor alpha production in Crohn's disease can be downregulated ex vivo by probiotic bacteria.

Background and aims: Tumour necrosis factor α (TNF-α) plays a key role in the pathogenesis of intestinal inflammation in Crohn’s disease. The effect of bacteria on TNF-α release by intestinal mucosa was investigated. Methods: Ileal specimens were obtained at surgery from 10 patients with Crohn’s disease (ileal stricture) and five disease controls undergoing right hemicolectomy (caecal cancer). Mucosal explants from each specimen were cultured for 24 hours with either non-pathogenic Escherichia coli, Lactobacillus casei DN-114001, L bulgaricus LB10, or L crispatus (each study contained blank wells with no bacteria). Tissue and bacterial viability was confirmed by lactate dehydrogenase (LDH) release and culture. Concentrations of TNF-α were measured in supernatants and the phenotype of the intestinal lymphocytes was analysed by flow cytometry. Results: Coculture of mucosa with bacteria did not modify LDH release. Release of TNF-α by inflamed Crohn’s disease mucosa was significantly reduced by coculture with L casei or L bulgaricus; changes induced by L crispatus or E coli were not significant. The effect of L casei and L bulgaricus was not prevented by protease inhibitors. Coculture with L casei and L bulgaricus reduced the number of CD4 cells as well as TNF-α expression among intraepithelial lymphocytes from Crohn’s disease mucosa. None of the bacteria induced changes in non-inflamed mucosa. Conclusions: Probiotics interact with immunocompetent cells using the mucosal interface and modulate locally the production of proinflammatory cytokines.

EURECCA colorectal: Multidisciplinary management: European consensus conference colon & rectum

BACKGROUND Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. METHODS The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and metastatic colorectal disease separately. Moreover, evidence based algorithms for diagnostics and treatment were composed which were also submitted to the Delphi process. RESULTS The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. CONCLUSIONS Multidisciplinary consensus on key diagnostic and treatment issues for colon and rectal cancer management using the Delphi method was successful. This consensus document embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

Low anterior resection syndrome and quality of life: an international multicenter study.

BACKGROUND: An increasing number of patients are surviving a diagnosis of rectal cancer. The majority of the patients are treated with the sphincter-sparing surgical procedure low anterior resection, and 50% to 90% of these patients experience bowel dysfunction, known as the low anterior resection syndrome. No previous studies have investigated the association between the low anterior resection syndrome and quality of life in an international setting with the use of a validated instrument for the classification of the low anterior resection syndrome. OBJECTIVE: The aim of this study was to investigate the association between quality of life and the low anterior resection syndrome in European patients who have had rectal cancer. DESIGN: The study was designed as an international cross-sectional study involving 5 centers in 4 European countries. PATIENTS: All patients had undergone low anterior resection for rectal cancer, had no stoma, had no dissemination or recurrence at the time of the study, and were at least 16 months past surgery. INTERVENTIONS: The patients received by mail the Low Anterior Resection Syndrome Score and the quality-of-life questionnaire EORTC QLQ-C30. MAIN OUTCOME MEASURES: Eight subscales were selected to be the focus of this study: global quality of life; physical, role, emotional, and social functioning; fatigue; constipation; and diarrhea. RESULTS: A total of 796 patients were included, which corresponds to a response rate of 75.0%. In comparison with patients without low anterior resection syndrome, patients with major low anterior resection syndrome fared substantially worse in all selected subscales (difference ≥ 10 points, p < 0.01), with the exception of constipation. LIMITATIONS: The cross-sectional design prevents an evaluation of causality. CONCLUSIONS: The quality of life of patients who have had rectal cancer is closely associated with the severity of the low anterior resection syndrome. Therefore, it is important that clinicians and researchers focus on this syndrome to improve the prevention and the treatment of bowel dysfunction and the information given to patients.

Outpatient Versus Hospitalization Management for Uncomplicated Diverticulitis A Prospective, Multicenter Randomized Clinical Trial (DIVER Trial)

Objective:We compare the results of 2 different strategies for the management of patients with uncomplicated left colonic diverticulitis and to analyze differences in quality of life and economic costs. Background:The most frequent standard management of acute uncomplicated diverticulitis still is hospital admission both in Europe and United States. Methods:This multicenter, randomized controlled trial included patients older than 18 years with acute uncomplicated diverticulitis. All the patients underwent abdominal computed tomography. There were 2 strategies of management: hospitalization (group 1) and outpatient (group 2). The first dose of antibiotic was given intravenously to all patients in the emergency department and then group 1 patients were hospitalized whereas patients in group 2 were discharged. The primary end point was the treatment failure rate of the outpatient protocol and need for hospital admission. The secondary end points included quality-of-life assessment and evaluation of costs. Results:A total of 132 patients were randomized: 4 patients in group 1 and 3 patients in group 2 presented treatment failure without differences between the groups (P = 0.619). The overall health care cost per episode was 3 times lower in group 2, with savings of &OV0556;1124.70 per patient. No differences were observed between the groups in terms of quality of life. Conclusions:Outpatient treatment is safe and effective in selected patients with uncomplicated acute diverticulitis. Outpatient treatment allows important costs saving to the health systems without negative influence on the quality of life of patients with uncomplicated diverticulitis. Trial registration ID: EudraCT number 2008-008452-17.

International Validation of the Low Anterior Resection Syndrome Score

Objective:The aims of this study were to investigate the convergent and discriminative validity and reliability of the low anterior resection syndrome (LARS) score in an international setting. Background:The LARS score is a simple self-administered questionnaire measuring bowel dysfunction after rectal cancer surgery. The score is intended to be commonly used in international research and clinical practice in the future. Therefore, a thorough validation in an international setting is of utmost importance. Methods:The LARS score was translated using methods in keeping with current international recommendations. A total of 801 patients operated for rectal cancer in Sweden, Spain, Germany, and Denmark completed the LARS score questionnaire, including an anchor question assessing the impact of bowel function on quality of life. A subgroup of 218 patients completed the LARS score twice. Data were analyzed per country. Results:The LARS score has demonstrated a high convergent validity in terms of a high correlation between LARS score and quality of life (P < 0.001). Sensitivity ranged from 67.7% to 88.3% and specificity from 58.1% to 86.3%. The LARS score was able to discriminate between groups of patients differing with regard to radiotherapy, surgery, and age (P < 0.05). The score also demonstrated high reliability at test-retest with narrow limits of agreement and no statistically significant difference between scores at the first and second test. Conclusions:The Swedish, Spanish, German, and Danish versions of the LARS score have proven to be valid and reliable tools for measuring LARS in European rectal cancer patients.

EPHB4 and Survival of Colorectal Cancer Patients

The family of receptor tyrosine kinases EPH and their Ephrin ligands regulate cell proliferation, migration, and attachment. An important role in colorectal carcinogenesis is emerging for some of its members. In this study, we evaluate the role of EPHB4 in colorectal cancer and its value as a prognostic marker. EPHB4 levels were assessed by immunohistochemical staining of tissue microarrays of 137 colorectal tumors and aberrant hypermethylation of the EPHB4 promoter was investigated using methylation-specific PCR. We found that EPHB4 expression is frequently reduced or lost in colorectal tumors. Patients with low EPHB4 tumor levels had significantly shorter survival than patients in the high EPHB4 group (median survival, 1.8 and >9 years, respectively; P < 0.01, log-rank test), and this finding was validated using an independent set of 125 tumor samples. In addition, we show that EPHB4 promoter hypermethylation is a common mechanism of EPHB4 inactivation. Moreover, reintroduction of EPHB4 resulted in a significant reduction in the clonogenic potential of EPHB4-deficient cells, whereas abrogation of EPHB4 in cells with high levels of this receptor lead to a significant increase in clonogenicity. In summary, we identified EPHB4 as a useful prognostic marker for colorectal cancer. In addition, we provide mechanistic evidence showing that promoter methylation regulates EPHB4 transcription and functional evidence that EPHB4 can regulate the long-term clonogenic potential of colorectal tumor cells, revealing EPHB4 as a potential new tumor suppressor gene in colorectal cancer.

EURECCA colorectal: Multidisciplinary Mission statement on better care for patients with colon and rectal cancer in Europe

BACKGROUND Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. METHODS The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. RESULTS The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. CONCLUSIONS It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

Experts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: Science, opinions and experiences from the experts of surgery

The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?

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.

Consensus statementExperts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: Science, opinions and experiences from the experts of surgery

The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?