Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation.

Mesothelial cells form the mesothelium, a simple epithelium lining the walls of serous cavities and the surface of visceral organs. Although mesothelial cells are phenotypically well characterized, their immunoregulatory properties remain largely unknown, with only two studies reporting their capacity to inhibit T cells through TGF-ß and their consumption of L-arginine by arginase-1. Whether human mesothelial cells can suppress other immune cells and possess additional leukosuppressive mechanisms, remain to be addressed to better delineate their therapeutic potential for cell therapy. Herein, we generated secretomes from omental mesothelial cells (OMC) and assess their capacity to inhibit lymphocytes proliferation, suppress activated T and B cells, as well as to modify macrophage activation markers. The secretome from mesenchymal stromal cells (MSC) served as a control of immuno-suppression. Although OMC and MSC were phenotypically divergent, their cytokine secretion patterns as well as expression of inflammatory and immunomodulary genes were similar. As such, OMC- and MSC-derived secretomes (OMC-S and MSC-S) both polarized RAW 264.7 macrophages towards a M2-like anti-inflammatory phenotype and suppressed mouse and human lymphocytes proliferation. OMC-S displayed a strong ability to suppress mouse- and human-activated CD19+/CD25+ B cells as compared to MSC-S. The lymphosuppressive activity of the OMC-S could be significantly counteracted either by SB-431542, an inhibitor of TGFß and activin signaling pathways, or with a monoclonal antibody against the TGFß1, ß2, and ß3 isoforms. A strong blockade of the OMC-S-mediated lymphosuppressive activity was achieved using L-NMMA, a specific inhibitor of nitric oxide synthase (NOS). Taken together, our results suggest that OMC are potent immunomodulators.

Feasibility of quantitative analysis of colonic perfusion using indocyanine green to prevent anastomotic leak in colorectal surgery.

BACKGROUND: The aim of this study was to quantify Fluorescence angiography with indocyanine green (ICG) in colorectal cancer anastomosis, determine influential factors in its temporary intensity and pattern, assessing the ability to predict the AL, and setting the cut-off levels to establish high- or low-risk groups. METHODS: Retrospective analysis of prospectively managed database, including 70 patients who underwent elective surgery for colorectal cancer in which performing a primary anastomosis was in primary plan. In all of them, ICG fluorescence angiography was performed as usual clinical practice with VisionSense™ VS Iridium (Medtronic, Mansfield, MA, USA), in Elevision™ IR Platform (Medtronic, Mansfield, MA, USA). Parameters measured at real time or calculated were T0, Tmax, ∆T, Fmax, %pos, Fpos, and Slope. RESULTS: 70 patients were included, 69 anastomosis were performed and one end colostomy. Arterial hypertension demonstrated higher Fmax, as well as the location of the anastomosis (the nearest to rectum, the most intensity detected). A statistical relationship was found between AL and the lower Fpos and Slope. The decision of changing the subjectively decided point of division did not demonstrate statistical difference on the further development of AL. All parameters were analyzed to detect the cut-off related with AL. Only in case of Fpos lower than 158.3 U and Slope lower than 13.1 U/s p-value were significant. The most valuable diagnostic parameter after risk stratification was the Negative Predictive Value. CONCLUSION: Quantitative analysis of ICG fluorescence in colorectal surgery is safe and feasible to stratify risk of AL. Hypertension and location of anastomosis influence the intensity of fluorescence at the point of section. A change of division place should be considered to avoid AL related to vascular reasons when intensities of fluorescence at the point of section is lower than 169 U or slopes lower than 14.4 U/s.

Réplica a la carta al director "Discrepancias en el análisis de la frecuencia, tipos de complicación y costes económicos en los pacientes ectópicos de cirugía general y digestiva" / Reply to the letter "Discrepancies in analysis of frequency, type of complications and economic costs of outlying patients in general and digestive surgery"

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Análisis de la frecuencia, tipos de complicación y costes económicos en los pacientes ectópicos de cirugía general y digestiva / Analysis of frequency, type of complications and economic costs of outlying patients in general and digestive surgery

Introducción: El descenso de camas disponibles y el aumento de la presión de Urgencias provocan que algunos pacientes sean ingresados en salas con camas libres pertenecientes a otros servicios (llamados pacientes ectópicos). El objetivo de este artículo es analizar la frecuencia, los tipos de complicación y los costes en los pacientes ectópicos. Métodos: Estudio retrospectivo de cohortes de pacientes ingresados a cargo de cirugía general y digestiva durante 2015 (fuente: Conjunto Mínimo Básico de Datos y contabilidad analítica). Comparamos las complicaciones, las estancias, los costes y las consecuencias de las complicaciones en todos los ectópicos, frente a un muestreo aleatorio de tantos pacientes no ectópicos como ectópicos ingresados en la misma fecha y con igual GRD. Se excluyen los 13 ectópicos sin par en los no ectópicos. Resultados: De un total de 2.915 pacientes, 363 (12,45%) fueron ectópicos. Se analizan un total de 350 ectópicos frente a 350 no ectópicos. No hubo diferencias significativas en las complicaciones (9,4 vs. 8,3%), las estancias (4,33 vs. 4,65 días) ni el coste (3.034,12 vs. 3.223,27 €). Los hombres ectópicos presentan un riesgo significativamente mayor de complicaciones respecto a las mujeres (RR = 2,10). Los ectópicos presentaron complicaciones a partir de 2,5 o más días como ectópicos. Conclusiones: Al necesitar ingresos ectópicos, seleccionando pacientes de baja complejidad, no aumentamos las complicaciones ni sus consecuencias (ingresos en la UCI, reingresos, reintervenciones o mortalidad), estancias o costes. Solo en caso de prolongar la estancia ectópica más de 2,5 días, o en varones, pueden aparecer más complicaciones, por lo que deberían evitarse ectópicos varones, en general, y plantearse su traslado si se prevé una estancia más allá de 2,5 días

Introduction: The shortage of available beds and the increase in Emergency Department pressure can cause some patients to be admitted in wards with available beds assigned to other services (outlying patients). The aim of this study is to assess the frequency, types of complications and costs of outlying patients. Methods: Using a retrospective cohort model, we analysed the 2015 general and digestive surgery records (source: Minimum Basic Data Set and economic database). After selecting all outlying patients, we compared the complications, length of stay, costs and consequences of complications against a randomized sample of non-outlying patients with the same DRG and date of episode for every outlying patient, obtaining one non-outlying patient for each selected outlying patient. Thirteen outlying patients with no non-outlying patient pair were excluded from the study. Results: From a total of 2,915 patients, 363 (12.45%) were outlying patients. A total of 350 outlying patients were analysed versus 350 non-outlying patients. There were no significant differences in complications (9.4 vs. 8.3%), length of stay (4.33 vs. 4.65 days) or costs (€3,034.12 vs. €3,223.27). Outlying patients men presented a significantly higher risk of complications compared to women (RR = 2.10). Outlying patients presented complications after 2.5 or more days. Conclusions: When outlying admissions become necessary, the selection of patients with less complex pathologies does not increase complications or their consequences (ICU admissions, readmissions, reoperations or mortality), hospital stays or costs. Only in cases of prolonged outlying stays of more than 2.5 days, or in males, may more complications appear. Therefore, male outliers should be avoided in general, and patients should be transferred to the proper ward if a length of stay beyond 2.5 days is foreseen

Analysis of frequency, type of complications and economic costs of outlying patients in general and digestive surgery. / Análisis de la frecuencia, tipos de complicación y costes económicos en los pacientes ectópicos de cirugía general y digestiva.

INTRODUCTION: The shortage of available beds and the increase in Emergency Department pressure can cause some patients to be admitted in wards with available beds assigned to other services (outlying patients). The aim of this study is to assess the frequency, types of complications and costs of outlying patients. METHODS: Using a retrospective cohort model, we analysed the 2015 general and digestive surgery records (source: Minimum Basic Data Set and economic database). After selecting all outlying patients, we compared the complications, length of stay, costs and consequences of complications against a randomized sample of non-outlying patients with the same DRG and date of episode for every outlying patient, obtaining one non-outlying patient for each selected outlying patient. Thirteen outlying patients with no non-outlying patient pair were excluded from the study. RESULTS: From a total of 2,915 patients, 363 (12.45%) were outlying patients. A total of 350 outlying patients were analysed versus 350 non-outlying patients. There were no significant differences in complications (9.4 vs. 8.3%), length of stay (4.33 vs. 4.65 days) or costs (€3,034.12 vs. €3,223.27). Outlying patients men presented a significantly higher risk of complications compared to women (RR=2.10). Outlying patients presented complications after 2.5 or more days. CONCLUSIONS: When outlying admissions become necessary, the selection of patients with less complex pathologies does not increase complications or their consequences (ICU admissions, readmissions, reoperations or mortality), hospital stays or costs. Only in cases of prolonged outlying stays of more than 2.5 days, or in males, may more complications appear. Therefore, male outliers should be avoided in general, and patients should be transferred to the proper ward if a length of stay beyond 2.5 days is foreseen.

Profilaxis de la hernia paraestomal mediante malla de polipropileno en espacio preperitoneal / Prevention of parastomal hernia with a preperitoneal polypropelene mesh

OBJETIVO: Presentar nuestra experiencia en la implantación periestomal de malla de polipropileno en espacio preperitoneal como profilaxis de hernia paraestomal en colostomías terminales en pacientes intervenidos por neoplasia rectal. MÉTODOS: Desde enero de 2010 hasta marzo de 2014, 45 pacientes consecutivos afectados de neoplasia de recto que requirieron implantación de colostomía terminal definitiva fueron intervenidos y analizados. En todos ellos se implantó una malla de polipropileno profiláctica en espacio preperitoneal periestomal. Analizamos variables demográficas, aspectos técnicos y efectividad de la técnica así como complicaciones consecuentes. RESULTADOS: Se implantó malla profiláctica en 45 pacientes, 35 varones y 10 mujeres, con una media edad de 66,2 años (47-88) y un indice de masa corporal de 29,1 (20,4-40,6). Se intervinieron de manera programada y con idéntico protocolo 7 adenocarcinomas de recto medio, 36 de recto bajo, un melanoma de recto y un carcinoma de células escamosas de ano; realizándose una amputación abdominoperineal en 38 pacientes y resección anterior baja con colostomía terminal en 7 pacientes. La vía de abordaje fue laparotómica en 39 casos y laparoscópica en 6 casos, 2 de los cuales se convirtieron a laparotomía. La mediana del tiempo de seguimiento fue de 22 meses (2,1-53). Se evidenciaron 3 hernias paraestomales (6,6%), siendo un hallazgo radiológico durante tomografía computarizada de control. No hubo complicaciones asociadas a la colostomía ni a la implantación de la malla. CONCLUSIONES: La colocación de una malla de polipropileno en localización paraestomal preperitoneal es fácilmente reproducible, disminuyendo la incidencia de hernia paraestomal sin aumentar la morbilidad ni la mortalidad

OBJECTIVE: To show our results with the use of a polypropylene mesh at the stoma site, as prophylaxis of parastomal hernias in patients with rectal cancer when a terminal colostomy is performed. METHODS: From January 2010 until March 2014, 45 consecutive patients with rectal cancer, underwent surgical treatment with the need of a terminal colostomy. A prophylactic mesh was placed in a sublay position at the stoma site in all cases. We analyze Demographics, technical issues and effectiveness of the procedure, as well as subsequent complications. RESULTS: A prophylactic mesh was placed in 45 patients, 35 male and 10 females, mean age of 66.2 (47-88) and Body Mass Index 29.19 (20.4-40.6). A total of 7 middle rectal carcinoma, 36 low rectal carcinoma, one rectal melanoma and one squamous cell anal carcinoma were electively treated with identical protocol. Abdominoperineal resection was performed in 38 patients, and low anterior resection with terminal colostomy in 7. An open approach was elected in 39 patients and laparoscopy in 6, with 2 conversions to open surgery. Medium follow up was 22 months (2.1-53). Overall, 3 parastomal hernias (6.66%) were found, one of which was a radiological finding with no clinical significance. No complications related to the mesh or the colostomy were found. CONCLUSIONS: The use of a prophylactic polypropylene mesh placed in a sublay position at the stoma site is a safe and feasible technique. It lowers the incidence of parastomal hernias with no increased morbidity

Prevention of parastomal hernia with a preperitoneal polypropelene mesh.

OBJECTIVE: To show our results with the use of a polypropylene mesh at the stoma site, as prophylaxis of parastomal hernias in patients with rectal cancer when a terminal colostomy is performed. METHODS: From January 2010 until March 2014, 45 consecutive patients with rectal cancer, underwent surgical treatment with the need of a terminal colostomy. A prophylactic mesh was placed in a sublay position at the stoma site in all cases. We analyze Demographics, technical issues and effectiveness of the procedure, as well as subsequent complications. RESULTS: A prophylactic mesh was placed in 45 patients, 35 male and 10 females, mean age of 66.2 (47-88) and Body Mass Index 29.19 (20.4-40.6). A total of 7 middle rectal carcinoma, 36 low rectal carcinoma, one rectal melanoma and one squamous cell anal carcinoma were electively treated with identical protocol. Abdominoperineal resection was performed in 38 patients, and low anterior resection with terminal colostomy in 7. An open approach was elected in 39 patients and laparoscopy in 6, with 2 conversions to open surgery. Medium follow up was 22 months (2.1-53). Overall, 3 parastomal hernias (6.66%) were found, one of which was a radiological finding with no clinical significance. No complications related to the mesh or the colostomy were found. CONCLUSIONS: The use of a prophylactic polypropylene mesh placed in a sublay position at the stoma site is a safe and feasible technique. It lowers the incidence of parastomal hernias with no increased morbidity.