Pathophysiology of Crohn's disease inflammation and recurrence.

Chron's Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions influenced by a complex pathogenesis in which inflammation plays a key role. Crohn's disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a TH1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence.

The Role of Inflammation in Crohn's Disease Recurrence after Surgical Treatment.

INTRODUCTION: Postoperative recurrence after surgery for Crohn's disease (CD) is virtually inevitable, and its mechanism is poorly known. AIM: To review the numerous factors involved in CD postoperative recurrence (POR) pathogenesis, focusing on single immune system components as well as the immune system as a whole and highlighting the clinical significance in terms of preventive strategies and future perspectives. METHODS: A systematic literature search on CD POR, followed by a review of the main findings. RESULTS: The immune system plays a pivotal role in CD POR, with many different factors involved. Memory T-lymphocytes retained in mesenteric lymph nodes seem to represent the main driving force. New pathophysiology-based preventive strategies in the medical and surgical fields may help reduce POR rates. In particular, surgical strategies have already been developed and are currently under investigation. CONCLUSIONS: POR is a complex phenomenon, whose driving mechanisms are gradually being unraveled. New preventive strategies addressing these mechanisms seem promising.

The Role of Active Inflammation and Surgical Therapy in Crohn's Disease Recurrence.

An altered balance between effector and regulatory factors is supposed to sustain the tissue-damaging immune response in inflammatory bowel disease (IBD). Several studies demonstrate that severe active inflammation is a strong predictor for surgical complications and recurrence. Indeed, bowel resection in Crohn's disease (CD) patients has a high surgical recurrence rate. In this review, we examined the IBD inflammatory pathways, the current surgical treatments, and the almost inevitable recurrence. The question that might arise is if the cure of intestinal CD is to be found in the surgical approach. A selective search of two databases (PubMed and the Cochrane Library) has been carried out without considering a specific time horizon as inclusion criteria. The scope of this literature review was investigating on the role of inflammation in the management of CD. The following key words have been used to develop the query string: (i) inflammation; (ii) Crohn's disease; (iii) surgery; and (iv) postsurgical recurrence.

Switch From Twice-daily Tacrolimus to Once-daily, Prolonged-release Tacrolimus in Kidney Transplantation: Long-term Outcome.

BACKGROUND: One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety. METHODS: The aim of our study was to demonstrate the long-term efficacy and safety of switching from BDT to QDT in KT recipients. Preliminary results have already been published. Forty-one patients (34 men and 7 women), mean age at KT of 43.9 ± 12.7 years, underwent a 1:1 dose switch from BDT to QDT; the mean time from KT to switch was 36.6 ± 16.1 months. In our study population, 4 patients received a living donor KT and 2 received a second allograft. RESULTS: The mean follow-up was 86.8 ± 13 months from the switch and 126.2 ± 22.3 months from KT. Graft and patient survival rates were 90.2% and 95.1%, respectively. All patients maintained stable renal function during follow-up. During the first 3 months after the switch we observed a significant decrease in tacrolimus blood level (P = .0001). No significant differences were observed regarding tacrolimus dose before and after QDT introduction (P = not significant [NS]). Fourteen patients who stopped steroids under BDT treatment and 16 patients who stopped steroids after the switch are currently steroid-free. CONCLUSION: Our study showed safety and efficacy in switching from BDT to QDT. After early (<1 year) dose adjustment, tacrolimus blood levels remained stable throughout follow-up. Moreover, QDT represented a valid alternative for patients showing steroid side effects.