Ji Elizalde

Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy.

Objective Achalasia is a chronic motility disorder of the oesophagus for which laparoscopic Heller myotomy (LHM) and endoscopic pneumodilation (PD) are the most commonly used treatments. However, prospective data comparing their long-term efficacy is lacking. Design 201 newly diagnosed patients with achalasia were randomly assigned to PD (n=96) or LHM (n=105). Before randomisation, symptoms were assessed using the Eckardt score, functional test were performed and quality of life was assessed. The primary outcome was therapeutic success (presence of Eckardt score ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for re-treatment, lower oesophageal sphincter pressure, oesophageal emptying and the rate of complications. Results In the full analysis set, there was no significant difference in success rate between the two treatments with 84% and 82% success after 5 years for LHM and PD, respectively (p=0.92, log-rank test). Similar results were obtained in the per-protocol analysis (5-year success rates: 82% for LHM vs 91% for PD, p=0.08, log-rank test). After 5 years, no differences in secondary outcome parameter were observed. Redilation was performed in 24 (25%) of PD patients. Five oesophageal perforations occurred during PD (5%) while 12 mucosal tears (11%) occurred during LHM. Conclusions After at least 5 years of follow-up, PD and LHM have a comparable success rate with no differences in oesophageal function and emptying. However, 25% of PD patients require redilation during follow-up. Based on these data, we conclude that either treatment can be proposed as initial treatment for achalasia. Trial registration numbers Netherlands trial register (NTR37) and Current Controlled Trials registry (ISRCTN56304564).

Improving safety of autologous haematopoietic stem cell transplantation in patients with Crohn's disease

Objective To evaluate the feasibility and toxicity of autologous haematopoietic stem cell transplantation (HSCT) for the treatment of refractory Crohns disease (CD). Design In this prospective study, patients with refractory CD suffering an aggressive disease course despite medical treatment, impaired quality of life and in whom surgery was not an acceptable option underwent HSCT. Toxicity and complications during the procedure and within the first year following transplantation were evaluated, along with the impact of the introduction of supportive measures on safety outcomes. Results 26 patients were enrolled. During mobilisation, 16 patients (62%) presented febrile neutropaenia, including one bacteraemia and two septic shocks. Neutropaenia median time after mobilisation was 5 days. 5 patients withdrew from the study after mobilisation and 21 patients entered the conditioning phase. Haematopoietic recovery median time for neutrophils (>0.5×109/L) was 11 days and for platelets (>20×109/L) 4 days. Twenty patients (95%) suffered febrile neutropaenia and three patients (27%) presented worsening of the perianal CD activity during conditioning. Among non-infectious complications, 6 patients (28.5%) presented antithymocyte globulin reaction, 12 patients (57%) developed mucositis and 2 patients (9.5%) had haemorrhagic complications. Changes in supportive measures over the study, particularly antibiotic prophylaxis regimes during mobilisation and conditioning, markedly diminished the incidence of severe complications. During the first 12-month follow-up, viral infections were the most commonly observed complications, and one patient died due to systemic cytomegalovirus infection. Conclusions Autologous HSCT for patients with refractory CD is feasible, but extraordinary supportive measures need to be implemented. We suggest that this procedure should only be performed in highly experienced centres.

Anemia Worsens Hyperdynamic Circulation of Patients with Cirrhosis and Portal Hypertension

This retrospective cohort study was aimed atinvestigating the effects of anemia on the hemodynamicdisturbances associated with portal hypertension. Inall, 202 consecutive nontreated portal-hypertensive patients referred for evaluation to our HepaticHemodynamic Laboratory were included. Compared to thenonanemic patients, anemic cirrhotic patients had anincreased cardiac output (7.9 ± 1.9 vs 7.1± 2 liters/min, P < 0.01), and a decreased mean arterialblood pressure (82 ± 11 vs 94 ± 13 mm Hg,P < 0.0001) and systemic vascular resistance (838± 235 vs 1102 ± 356dyn/sec/cm5, P < 0.0001). Similar resultswere obtained when Child A or Child B-C patients were analyzedseparately. Multivariate logistic regression disclosedthat hemoglobin concentration, in addition to age, sexazygos blood flow, and albumin concentration, was anindependent factor influencing the degree of systemicvasodilation in cirrhotic portal-hypertensive patients.This study discloses that anemia worsens thehyperdynamic circulation associated with portalhypertension. Since hemoglobin concentration may change withtime, this parameter should be taken into account whenevaluating hemodynamics in portal-hypertensivepatients.

Evaluation of PARVG located on 22q13 as a candidate tumor suppressor gene for colorectal and breast cancer

Colorectal cancer (CRC) and breast cancer constitute common neoplasms in Western countries and leading causes of cancer-related death. Development and progression of both malignancies occur as a multistep process, requiring the activation of oncogenes and the inactivation of several tumor suppressor genes. Our group has recently identified a minimal region of deletion on 22q13 involved in CRC and breast cancer patients, which is highly indicative of the existence of a tumor suppressor gene (or genes). We performed mutation analysis of the PARVG gene, one of the genes present on the 22q13 region of interest, which has been previously demonstrated to have a reduced expression in some cancer cell lines. We have identified several DNA variants that are not compatible with pathogenic mutations. Accordingly, PARVG appears not to be a tumor suppressor gene involved in CRC and breast cancer development and progression.

Evaluación de la eficacia y eficiencia de una unidad multidisciplinaria para la atención de pacientes con cáncer colorrectal

Introduccion . El aumento de la complejidad del abordaje diagnostico-terapeutico de los pacientes con cancer colorrectal (CCR) hace aconsejable su atencion en unidades multidisciplinarias especializadas. El objetivo de este estudio fue evaluar la eficacia y la eficiencia de una unidad de cancer colorrectal (UCCR) en el abordaje diagnostico-terapeutico de estos pacientes. Pacientes Y Metodos . Se han seleccionado dos grupos de 50 pacientes con cancer de colon atendidos en nuestro centro antes y despues de la implementacion de la UCCR. Se ha analizado el cumplimiento del protocolo asistencial en relacion con la estadificacion del tumor, el tratamiento quirurgico y complementario, el seguimiento, el intervalo hasta la terapia, la estancia hospitalaria, la morbilidad y mortalidad inmediata, y la duracion global del proceso diagnostico-terapeutico. Ademas, se ha evaluado la carga asistencial y se ha realizado un analisis de minimizacion de costes. Resultados . La UCCR ha permitido reducir el intervalo hasta la cirugia (20,3 ± 12,0 frente a 28,9 ± 20,4 dias; p = 0,05), la estancia hospitalaria (9,8 ± 7,7 frente a 14,5 ± 9,3 dias; p = 0,01), el tiempo transcurrido hasta el inicio del tra-tamiento adyuvante (29,4 ± 10,2 frente a 39,7 ± 19,8 dias; p = 0,03), y la duracion global del proceso (60,4 ± 23,8 frente a 82,1 ± 46,1 dias; p = 0,05), lo que supone un ahorro de 978,85 euros por paciente. Esta mejora ha tenido lugar a pesar del incremento de la carga asistencial (24% en 5 anos en relacion con el numero de ingresos) y no ha afectado la morbilidad (26 frente a 24%; NS) ni la mortalidad inmediata (6 frente a 4%; NS). Conclusion . Las unidades multidisciplinarias especializadas favorecen un abordaje mas eficaz y eficiente de los pacientes con cancer de colon.

Mo1874 Long-Term Results of the European Achalasia Trial: Pneumatic Dilation Versus Laparoscopic Heller Myotomy

G A A b st ra ct s patients were included. The average number of esophageal biopsies per gastroscopy was 3.7 ± 2.6 (extremes = 1; 8). The esophageal site from which biopsies were taken was unknown in 33.3% (n = 11), at only one level in 24.2% (n = 8), and at least at two levels in 42.4% (n = 14) of cases. The number of biopsies per site was identified in 70% (n = 23) of the reports. In total, 30.4% (n = 7) of the reports were done in accordance with the consensus recommendations (at least 2 identified sites in the esophagus with at least 2 biopsies per site). CONCLUSION: If the total number of biopsies done for the diagnosis of EoE seemed sufficient, the identification of biopsy levels and the number of biopsies per site was not. Only 30% of endoscopy reports respected the consensus guidelines. A better identification of biopsy sites is possible without prolonging the endoscopy time and would contribute to improving the diagnosis. 1 Liacouras CA, Furuta C, et al. Eosinophilic esophagitis: Updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128:3-20.

Sa1927 Significant Genetic Variability Associated With the Evolution of Gastric Cancer Precursor Lesions in a Spanish Population

Objective Preoperative chemoradiotherapy has recently become common practice in treatment of esophageal cancer with a gain in 5-year survival of 10-15%. However, a significant proportion of patients do not respond well and experiencing unnecessary severe side-effects. Accurate risk-stratification of patients using informative biomarkers before therapy may help to avoid unnecessary morbidity due to ineffective treatment. The aim of this study was to investigate the correlation between the expression of SOX2 and P53 in pre-treatment tumor biopsies and grade of pathological tumor response in resected specimen of patients with esophageal adenocarcinoma (EAC) treated with neoadjuvant chemoradiotherapy (nCRT). Methods All EAC patients who received nCRT according to the CROSS regimen followed by esophagectomy, between January 2003 and July 2011 at the Erasmus University Medical Center, were included. SOX2 and P53 protein expression was visualized by immunohistochemistry on all pre-treatment tumor biopsies and scored independently by two investigators who were blinded for clinical outcome. Aberrant expression was defined as negative expression of SOX2 and overexpression or complete loss of P53 expression. The overall Tumor Regression Grade (TRG) was evaluated using the modified Mandard scoring system. Patients with TRG 1 or TRG 2 were classified as major responders (ie, 10% of tumor cells remaining). Results In total 77 patients were included. Forty (53%) patients had a major pathological response (TRG 1-2) and 37 (47%) a minor response (TRG 3-4). In pre-treatment biopsies aberrant SOX2 and P53 expression was seen in 40% (31/77) and 83% (64/77), respectively. A major response was significantly associated with an aberrant SOX2 expression (OR 3.9, 95% CI: 1.5 10.2, p=0.005) and aberrant p53 expression (OR 4.5, 95% CI: 1.15 18.2, p=0.031). Aberrant expression of both biomarkers increased the probability of a major response in the individual patient (OR of 5.6; 95% CI: 2.1 14.9, p= 0.001), with a sensitivity of 68%, specificity of 73% and a positive predictive value of 73%. Conclusion SOX2 and P53 expression in the pre-treatment biopsies predict response to nCRT in patients with EAC. These biomarkers might help to identify patients who are likely to benefit most from this multimodality treatment.

Mo1176 Autologous Hematopoietic Stem Cell Transplantation in Refractory Crohn's Disease: Feasibility and Toxicity

G A A b st ra ct s diagnosis of cancer was 10 (range 1-38). IMM used after the diagnosis of cancer included thiopurines in 12 (AZA n= 8 ; 6MP n4), anti-TNFs in 3 (ADA n=.2; local IFX n=1). Among the 15 IBD patients treated with IMM after the diagnosis of neoplasia, cancer involved: thyroid (n=4), skin (n=2; 1 basal cell carcinoma, 1 spinal cell carcinoma); breast (n=2), colon (n=2), prostatic cancer (n=2) lymphoma (HL n=1), seminoma (n=1), carcinoid of the appendix (n=1). The time interval between the diagnosis of cancer and IMM was 6 yrs (range 1-26). After a median follow up from the diagnosis of cancer of 10 yrs (range 3-30), none of the 15 IBD patients treated with IMM after the diagnosis of cancer showed recurrence of cancer, or had a cancer-related death. Death was observed in 1 CD patient, due to cirrhosis. CONCLUSIONS. In a preliminary retrospective study, treating IBD patients with thiopurines or anti-TNFs after a diagnosis of cancer currently appeared not to determine a recurrence of the neoplastic disease. Larger prospective longitudinal studies are needed to further address this open issue in IBD.