Complete histologic normalisation is associated with reduced risk of relapse among patients with ulcerative colitis in complete endoscopic remission

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153611/1/apt15568.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153611/2/apt15568_am.pd

Mucosal Healing in Ulcerative Colitis: A Comprehensive Review

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice. The basic mechanisms behind colonic injury and MH are covered, highlighting the pathways through which different drugs exert their effect towards reducing inflammation and promoting epithelial repair. A comprehensive review of the evidence for approved drugs for UC to achieve and maintain MH is provided, including a section on the pharmacokinetics of anti-tumor necrosis factor (TNF)-alpha drugs. Currently approved drugs with proven efficacy in achieving MH in UC include salicylates, corticosteroids (induction only), calcineurin inhibitors (induction only), thiopurines, vedolizumab and anti-TNF alpha drugs (infliximab, adalimumab, and golimumab). MH is of crucial relevance in the outcomes of UC, resulting in lower incidences of clinical relapse, the need for hospitalization and surgery, as well as reduced rates of dysplasia and colorectal cancer. Finally, we present recent evidence towards the need for a more strict definition of complete MH as the preferred endpoint for UC patients, using a combination of both endoscopic and histological findings.info:eu-repo/semantics/publishedVersio

Aspects anatomopathologiques des maladies inflammatoires chroniques intestinales chez l'homme et effet d'une carence en donneurs de méthyles sur le développement intestinal chez l'animal

Inflammatory bowel diseases (IBD) are very frequent. Pathological examination in IBD management is important for the diagnosis and for the follow-up of the disease. In this study we show that submucosal plexitis in the proximal resection margins and early surgical revision after the first ileocecal resection are associated with CD recidive requiring surgical treatment. It could be very important in order to stratify patients according to their risk, identifying those who can benefit from aggressive medication regimen, possibly modifying the natural course of CD. IBD pathogenesis is not completely clarified. We show the importance of molecules as PPAR gamma and NRLP6 in intestinal homeostasis : a reduced expression of PPAR gamma and NRLP6 could predispose of IBD. The same observation is made for methyl donor deficiency (MDD): methyl deficient diet aggravates experimental colitis induced by Dextran Sodium Sulfate in rat. To understand how MDD could play a part in Crohn?s disease pathogenesis, we investigated whether MDD may affect development and functions of small intestine in rat pups from dams subjected to the MDD during gestation and lactation. MDD has dual effects on small intestine by producing dramatic effects on enterocyte differentiation and barrier function in rats. Our observations could explain how vitamin B12 and folate deficiency can play a role in Crohn?s disease developmentLes maladies inflammatoires chroniques intestinales (MICI) représentent un groupe de pathologies fréquentes. L'apport de l'analyse anatomopathologique des prélèvements dans le cadre de ces pathologies représente un rôle non négligeable dans la prise en charge des patients atteints par ces maladies. Nous avons montré que la présence de lésions de pléxite sur la limite proximale de pièces de résection iléocaecale relative à une atteinte par la maladie de Crohn était prédictive d'une rechute de la maladie nécessitant une seconde chirurgie, pouvant ainsi guider le clinicien pour une prise en charge thérapeutique plus adaptée. D'un point de vue physiopathologique, les MICI sont des maladies dont la pathogénie reste encore en partie à élucider. Dans ce travail nous avons montré l'importance de certains acteurs comme PPAR gamma et NRLP6 dans le maintien d'un fonctionnement normal de l'intestin. Il en est de même pour une carence en donneurs de méthyles : nous avons démontré qu'une telle carence aggravait les lésions de colite induites par DSS (Dextran Sulfate Sodium) chez le rat. Afin de mieux comprendre comment une carence en donneurs de méthyles pouvait intervenir dans la pathogénie de la maladie de Crohn, nous avons étudié l'impact de cette carence sur le fonctionnement et le développement de l'intestin grêle chez des ratons issus de mères carencées en folate et en vitamine B12 durant la gestation et l'allaitement, démontrant ainsi qu'un déficit en donneurs de méthyles entraîne des conséquences sur le fonctionnement de l'intestin grêle, pouvant ainsi créer un état de prédisposition au développement de la maladie de Croh

Assessment of Apoptosis by Immunohistochemistry to Active Caspase-3, Active Caspase-7, or Cleaved PARP in Monolayer Cells and Spheroid and Subcutaneous Xenografts of Human Carcinoma

Immunohistochemistry to active caspase-3, recently recommended for apoptosis detection, is inappropriate to detect apoptosis involving caspase-7. Cleavage of poly-ADP-ribose polymerase 1 (PARP-1), a major substrate of both caspases, is a valuable marker of apoptosis. Apoptosis evaluation induced in vitro either by paclitaxel or by photodynamic treatment (PDT) with Foscan in HT29 or KB monolayer cells and HT29 spheroids yielded a close percentage of labeled cells whatever the antibody used, whereas in control specimens, cleaved PARP (c-PARP) immunostaining failed to detect apoptosis as efficiently as active caspase-3 or -7 immunostaining. Studies in MDA-MB231 monolayer cells and HT29 xenografts either subjected or not subjected to Foscan-PDT resulted in a significant higher number of active caspase-3–labeled cells, although immunofluorescence analysis showed c-PARP and active caspase-3 perfectly colocalized in tumors. A restricted expression of c-PARP was obvious in the greater part of caspase-3 expressing cells from control tumor, whereas photosensitized tumors showed a higher number of cells expressing large fluorescent spots from both active caspase-3 and c-PARP. These results support the assumption that c-PARP expression was dependent on treatment-induced apoptosis. The absence of caspase-7 activation in some caspase-3–expressing cells undergoing Foscan-PDT shows the relevance of using antibodies that can discriminate caspase-dependent apoptotic pathways. (J Histochem Cytochem 57:289–300, 2009