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.
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.
Background/Objectives: The rising use of liver grafts from donation after circulatory death (DCD) has been enabled by advances in normothermic regional perfusion (NRP) and machine perfusion (MP) technologies. We aimed to identify predictive biomarkers in DCD grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). Methods: Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week post-transplant. Biomarkers linked with oxidative stress, hepatic injury, mitochondrial dysfunction, inflammation, regeneration, and autophagy were measured during NRP, end-ischemic MP, and one week post-transplant. Results: Arginase-1 (ARG-1) levels were consistently higher in discarded grafts and in recipients who later developed early allograft dysfunction (EAD). Specifically, ARG-1 levels at the end of MP correlated with markers of hepatic injury. Receiver operating characteristic analysis indicated that ARG-1 at the end of MP had a good predictive accuracy for EAD (AUC = 0.713; p = 0.02). Lipid peroxidation (TBARS) elevated at the start of NRP, declined over time, with higher levels in D-HOPE than in NMP, suggesting a more oxidative environment in D-HOPE. Metabolites like flavin mononucleotide (FMN) and NADH exhibited significant disparities between perfusion types, due to differences in perfusate compositions. Inflammatory biomarkers rose during NRP and NMP but normalized post-transplantation. Regenerative markers, including osteopontin and hepatocyte growth factor, increased during NRP and NMP and normalized post-transplant. Conclusions: ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.
28 December 2020 in Gastroenterology Research and Practice
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 Crohns 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) Crohns disease; (iii) surgery; and (iv) postsurgical recurrence.
The rising use of liver grafts from donation after circulatory death (DCD) has been enabled by advances in normothermic regional perfusion (NRP) and machine perfusion (MP) technologies. Our study aimed to identify predictive biomarkers in DCD liver grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week after transplantation. Biomarkers linked with oxidative stress, hepatic injury, mitochondrial dysfunction, inflammation, regeneration, and autophagy gene expression were measured during NRP, end-ischemic MP, and one week post-transplant. Arginase-1(ARG-1) levels were consistently higher in discarded grafts and recipients who later developed early allograft dysfunction (EAD). Specifically, ARG-1 levels at the end of ex-situ machine perfusion correlated significantly with other markers of hepatic injury. Receiver Operating Characteristic analysis indicated that ARG-1 at the end of MP had good predictive accuracy for EAD (AUC = 0.713 [95% CI: 0.538-1]; p = 0.02). Additionally, lipid peroxidation, measured by TBARS, was elevated at the start of NRP but declined over time, with higher levels in D-HOPE than in NMP, suggesting a more sustained oxidative environment. Metabolites like Flavin mononucleotide (FMN) and NADH exhibited significant disparities between perfusion types, due to differences in perfusate compositions. Inflammatory biomarkers rose during NRP and NMP but normalized post-transplantation. Regenerative markers, including osteopontin and hepatocyte growth factor, also increased during NRP and NMP and normalized after transplantation. In conclusion, ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.
The management of de novo kidney tumors (DKTs) after liver transplantation (LT) is challenging due to previous transplant surgery and calcineurin inhibitors (CNI)-related nephrotoxicity. Minimally invasive renal-sparing strategies like robot-assisted partial nephrectomy (RPN) are favored, but a transperitoneal approach may be limited by the previous transplant surgery and the location of the DKT; in such cases, CT-guided cryoablation may be an alternative option. In this retrospective cohort study, we aimed to compare RPN and cryoablation for the treatment of DKT in LT recipients. The primary endpoints were the efficacy (R0 resection in RPN, absence of the tumor at first follow-up for cryoablation) and the safety of the procedures (postoperative morbidity and increase in creatine level). The periprocedural costs and the oncologic efficacy (recurrence and overall survival) were the secondary endpoints. Twelve LT recipients (91.7% males, mean age 65 years) underwent RPN (n = 6) or cryoablation (n = 6) for DKT; the median interval between LT and diagnosis of DKT was 142.5 vs. 117.5 months, respectively. Efficacy was obtained in all patients after RPN and cryoablation. Postoperative morbidity was 16.7% in each group, and the postoperative increase in creatinine values was similar. Hospital stay was shorter following cryoablation vs. RPN (3.1 vs. 6.7 days; p = 0.03). The mean procedural costs were higher for RPN. There was no mortality and none of the patients had signs of recurrence after a median follow-up of 40.5 months. Both RPN and CT-guided cryoablation were safe and effective for the treatment of selected patients with DKT after LT. When applicable, cryoablation may be cost-effective and provide faster recovery.