Efecto sobre la colitis por diversión tras estimulación del asa eferente con probióticos previo al cierre de la ileostomía de protección en pacientes intervenidos de carcinoma colorrectal. Estudio prospectivo, randomizado, doble ciego

Abstract

Introduction The performance of a temporary ileostomy in patients operated on for colorectal carcinoma, by means of an anterior resection with total mesorectal excision, reduces the morbidity associated with anastomotic leak. However, reconstructive surgery is not risk-free. The incidence of complications following ileostomy closure, such as diversion colitis, small bowel obstruction, surgical wound infections, postoperative ileus, anastomotic leak, fistula, perforation, abscess, bleeding or hernia, ranges from 18% to 40%. Diversion colitis is a non-specific inflammation of a defunctionalised segment of the colon after a temporary stoma has been performed. This inflammation is associated with a change in the colonic flora, endoscopic changes, histological changes and an alteration of certain inflammatory serum biomarkers. This changes produces dysbacteriosis and atrophy of its villi and muscular layers in the excluded colon segment, as well as a loss of segmentary contractility that could produce a reduction in the ability for absorption. To avoid this, two lines of studies have been proposed; early closure of the loop ileostomy, which would be the best option, or late closure after stimulation of the efferent loop. Based on the need to return the excluded intestine to its function, pre-enabling it before surgery reconstruction and demonstrated bacterial dysbiosis, we decided to administer probiotics through the efferent loop. Probiotics are increasingly being applied in gastrointestinal pathology. They are non-pathogenic live bacteria, such as Lactobacillus, Bifidobacterium and Estreptococcus, which present antimicrobial and immunomodulatory activity and improve the intestinal barrier. Supplied in adequate amounts, they promote health benefits on the host. Hypothesis Preoperative stimulation of the efferent loop with probiotics prior to closure of the protective ileostomy in patients operated on colorectal carcinoma decreases the diversión colitis and, therefore, reduces the symptons associated with diversión colitis after restorative surgery. Objectives To evaluate the efficacy and safety of preoperative stimulation of the efferent loop with probiotics prior to closure of the protective ileostomy in patients operated on colorectal carcinoma and its effect on diversion colitis. Endoscopic and histological changes, biomarkers serological changes and postoperative ileus were evaluated. Results The incidence of postoperative ileus was similar in both groups. There were no significant differences with regard to need of a nasogastric tube, restoration of bowel function and duration of hospital stay. The comparative analysis showed a direct relationship between postoperative ileus after oncological surgery and postoperative ileus after reconstruction surgery, independently of stimulation with p = 0.005. A decrease in endoscopic and histological severity were observed in stimulated group. These results are statistically significant with a p<0,001 and a intense level association. A decrease in endoscopic findings (mucosal friability, mucous erosions, polyps, edema, erythema and stenosis) and in histological findings (follicular hyperplasia, eosinophils, cryptic abscesses, lymphocyte infiltration, plasma cell infiltration and architecture distortion) were observed in stimulated group. These results are statistically significant with a p<0,001 and a intense level association. In serological biomarkers study, a significant decrease in C-reactive protein (CRP), Neutrophil/lymphocyte ratio (NLR ratio) and monocyte/lymphocyte ratio (MRL ratio) and a significant increase in transferrin values and in the platelet/lymphocyte ratio (PLR) was observed in the stimulated group versus control group after stimulation with probiotics with a p <0.001. A normalization of CRP and transferrin levels was observed in the third month of follow-up after closure ileostomy, and NLR, MRL and PLR ratios were equal in both groups. Conclusions 1) Probiotic stimulation of the efferent loop is a safe and effective method; 2) It produces a decrease of the endoscopic and histological severity of colitis; 3) As well as, a decrease in symptoms in the short term after reconstructive surgery; 4) This procedure can be an alternative treatment in patients who surgical option is not feasible or available; 5) The endoscopic and histological severity of DC is associated with a greater alteration of inflammatory biomarkers in the blood; 6) The stimulation with probiotics prior to reconstructive surgery produces an early normalization of these parameters; 7) Postoperative ileus after closure ileostomy is independent of stimulation of the ileostomy with probiotics through the efferent loop; 8) There seem to be a relationship between PI after reconstruction and the previous existence of postoperative ileus after colorectal cancer surgery.