Involvement of MIR-126 and MMP9 in the Pathogenesis of Intra-Abdominal Fistulizing Crohn's Disease: A Brief Research Report.

Background: Intra-abdominal fistulas are complications that affect a significant proportion of Crohn's disease patients, often requiring surgery. The aim of the present work was to correlate the occurrence of intestinal fistulization to the clinico-pathological features of these patients and to the plasma levels of MMP9, a gelatinase involved in the pathophysiology of fistula formation, and of miR-126, appearing to modulate MMP9 expression. Methods: In a series of 31 consecutive Crohn's patients admitted to surgery due to therapeutic failure and/or complicated disease, we identified nine cases of abdominal fistulas, mainly entero-enteric fistulas. MMP9 protein was determined in plasma and at the intestinal level using immunometric assays. Circulating miR-126 was also measured in all plasma samples by real-time PCR. Results: Comparing patients with and without intra-abdominal fistulas, we did not observe differences in terms of age, gender, disease location and duration, number of previous surgeries and pre-biologic medications. However, cases with intra-abdominal fistulas had a significantly higher CDAI (p < 0.0001) and a significantly lower circulating miR-126 (p < 0.05). Patients with intra-abdominal fistulas had also a significantly higher amount of circulating MMP9 (p < 0.0001) and this data was correlated with an increased expression of MMP9 protein in the mucosa and with reduced levels of circulating miR-126. Receiver operating characteristic (ROC) analysis pointed out the ability of circulating MMP9 to discriminate patients with and without intra-abdominal fistulas. Conclusions: These data confirm that circulating MMP9 can be used for the identification of cases with intra-abdominal fistulas and suggest that miR-126 may be also involved in the pathogenesis of this complication and that it may be further investigated as a new therapeutic strategy or for monitoring therapeutic response in these patients.

Anastomosis configuration and technique following ileocaecal resection for Crohn's disease: a multicentre study.

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade ≥ 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade ≥ 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade ≥ 3, a penetrating phenotype of disease and ileo-colonic distribution of CD.

Effect of long-lasting nutritional prehabilitation on postoperative outcome in elective surgery for IBD.

BACKGROUND & AIMS: Preoperative patient care optimisation appears to be crucial for obtaining good surgical outcomes. Enhanced Recovery After Surgery (ERAS) underlines the necessity to recognize and treat malnutrition perioperatively and to prehabilitate with interventions that can modulate the lean body mass before and after surgery. This procedure has been extensively reported in colorectal cancer patients but in Inflammatory Bowel Disease (IBD) it has not yet been clearly evaluated. The aim of this study was to implement the perioperative nutritional items in surgical Crohn's disease (CD) and ulcerative colitis (UC) patients electively operated in an ERAS setting, thus to clarify the impact of a long-lasting prehabilitation program in IBD. METHODS: Consecutive adult patients (age ≥18) were included as soon as scheduled for elective surgery for CD or UC. The nutritional intervention included personalized dietary counseling and oral nutritional supplements when necessary. Data prospectively recorded in each phase were: FFM, FM, FFMI and phase angle detected with BIVA, weight, BMI, unintended weight loss, DASI, energy and nutritional intake, gastrointestinal symptoms and bowel functions. Nutritional risk was detected according to the NRS 2002 screening tool. The impact of early oral nutrition on postoperative recovery was analysed. RESULTS: A total of 61 IBD patients (45 CD and 16 UC) were included. Muscle wasting was present at baseline assessment in 28% of cases, significantly associated with the presence of ileostomy (p < 0.011) and of a previous IBD surgery (p < 0.011). During the preoperative phase, there was a significant improvement in weight, BMI, FFM (CD p = 0.035; UC p = 0.017), FFMI (CD ns; UC p = 0.011) and phase angle (CD p = 0.014; UC p = 0.027). During the intra-hospital phase, weight and FFM decreased due to the catabolic effect of surgery, but in the whole perioperative period, both CD and UC patients did not change significantly in terms of body composition. Patients with earlier resumption of oral feeding had a significantly shorter hospital stay and a faster recovery of bowel function with no significant relationship with early postoperative complications. CONCLUSIONS: Nutritional prehabilitation positively modulated the body composition of IBD patients scheduled for elective surgery and therefore could represent a beneficial strategy to attenuate the impact of the surgical stress response on lean tissue in an ERAS setting. This effect is even more evident in high nutritional risk patients. Early postoperative oral feeding seems feasible and well tolerated in IBD. This approach positively influences the restoration of bowel function and the duration of hospital stay.