A 72-year-old woman presented with symptomatic anemia without abdominal symptoms. She had no history of abdominal surgery or use of non-steroidal anti-inflammatory drugs. Enhanced computed tomography of the abdomen revealed swelling of multiple intraperitoneal lymph nodes and a high density of mesenteric adipose tissue. Fluorodeoxyglucose (FDG-) positron emission tomography showed high FDG accumulation at the intraperitoneal lymph nodes. Double-balloon enteroscopy detected severe stenosis with an annular ulcer in the lower ileum. She was diagnosed with ileal follicular lymphoma based on histologic examination and fluorescence in situ hybridization analysis of the biopsy specimen. The ileal ulcer was successfully treated by chemotherapy with rituximab and bendamustine for 1 year. We strongly recommend consideration of gastrointestinal follicular lymphoma in the differential diagnosis of annular ulcers in the small intestine.
Little is known about the efficacy and safety of infliximab for ulcerative colitis refractory to tacrolimus. The aim of this study was to evaluate the efficacy and safety of infliximab in the induction of remission in ulcerative colitis patients with persistent symptoms despite tacrolimus therapy.We report a retrospective, observational, single-center case series of 12 consecutively enrolled patients with ulcerative colitis refractory to tacrolimus that received infliximab therapy for the induction of remission. Eight patients received a single infusion of infliximab, and four received two or more infusions. Median follow-up duration was 16.0 months (range, 1.6-41.4 months). The clinical response was evaluated based on a modified Truelove-Witts severity index.Six patients (50.0%) achieved clinical remission within 30 days. Overall cumulative colectomy-free survival was estimated to be 58.3% at 41.4 months. Adverse events included an elevation of liver enzymes (1/12; 8.3%) and a mild infusion reaction (1/12; 8.3%). No mortality occurred.Infliximab can induce remission in patients with ulcerative colitis who do not tolerate or respond to tacrolimus therapy.
Abstract Lipocalin 2 (Lcn2), also called neutrophil gelatinase B-associated lipocalin (NGAL), is an anti-microbial peptide originally identified in neutrophil granules. Although Lcn2/NGAL expression is increased in the inflamed intestinal tissues of patients with inflammatory bowel disease, the role of Lcn2/NGAL in the development of intestinal inflammation remains unclear. Here we investigated the role of Lcn2/NGAL in intestinal inflammation using a spontaneous mouse colitis model, interleukin-10 knock out (IL-10 KO) mice. Lcn2 expression in the colonic tissues of IL-10 KO mice increased with the development of colitis. Lcn2/IL-10 double-KO mice showed a more rapid onset and development of colitis compared to IL-10 KO mice. Lcn2 enhanced phagocytic bacterial clearance in macrophages in vitro after infection with Escherichia coli . Transfer of Lcn2-repleted macrophages prevented the development of colitis in Lcn2/IL-10 double-KO mice in vivo . Our findings revealed that Lcn2 prevents the development of intestinal inflammation. One crucial factor seems to be the enhancement of phagocytic bacterial clearance in macrophages by Lcn2.
Background and study aims Mucosal healing (MH) is associated with clinical outcome in ulcerative colitis (UC) patients. In most clinical trials, a Mayo endoscopic subscore (MES) of 0 or 1 is defined as MH. However, several recent studies have reported that clinical outcome is different between UC patients with MES 0 and those with MES 1. In addition, the MES is subjective and may differ among endoscopists. Therefore, a repeatable and objective scoring system is required to distinguish MES 0 from MES 1, even in clinically quiescent UC. Here, we assessed the usefulness of new image-enhancing endoscopic technology, the i-scan TE-c, to quantitatively evaluate colonic inflammation in patients with quiescent UC. Methods We retrospectively reviewed the data from 52 UC patients in clinical remission who had undergone routine colonoscopy with standard white light. The white-light images were reassessed using the new system, and the degree of colonic mucosal inflammation was quantified according to the MAGIC (Mucosal Analysis of Inflammatory Gravity by i-scan TE-c Image) score. We used the i-scan TE-c system to investigate the association among the MAGIC score, MES, and histologic activity (Geboes score). Results The MAGIC score was significantly higher in the MES 1 group than in the MES 0 group ( P = 0.0034). The MAGIC score significantly correlated with the Geboes score ( P = 0.015). Conclusions Our novel image-enhancing endoscopic system was useful for objective and quantitative evaluation of MH in patients with quiescent UC. Further clinical studies using this imaging system are required to confirm its clinical benefit for the management of UC patients.
Tacrolimus is a novel immunomodulator for inflammatory bowel diseases. Immunosuppressive effects of tacrolimus on T cells are well known; however, the effects of tacrolimus on macrophages remain unclear. The aim of this study was to investigate the effects of tacrolimus on activated macrophages and to examine its efficacy in murine colitis models.Proinflammatory cytokine production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages of IL-10-knockout (KO) mice with and without tacrolimus was measured. We investigated the effects of tacrolimus on nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and caspase activation in macrophages and the induction of apoptosis in macrophages in vitro and examined the in vivo apoptotic effect of tacrolimus on colonic macrophages in IL-10-KO mice. We evaluated the effect of the rectal administration of tacrolimus on colonic inflammation in IL-10-KO mice and dextran sulfate sodium (DSS)-induced colitis in CB.17/SCID mice.Proinflammatory cytokine production from tacrolimus-treated macrophages was significantly lower than that from untreated cells. Tacrolimus suppressed LPS-induced activation of both NF-κB and MAPK in macrophages and induced apoptosis of macrophages via activation of caspases 3 and 9. Rectal administration of tacrolimus evoked apoptosis of colonic macrophages in IL-10-KO mice. Moreover, the rectal administration of tacrolimus ameliorated colitis in IL-10-KO mice and DSS-induced colitis in CB.17/SCID mice. Gene expression of inflammatory cytokines in colonic mucosa was significantly lower in tacrolimus-treated mice than in untreated mice.Tacrolimus suppresses the function of activated macrophages and promotes their apoptosis, which may lead to the amelioration of colonic inflammation.
Science S81Conclusions: These data show a strong correlation of inflammatory responses between the colitis and radiationinduced models of GI injury, with a common TNF-mediated, neutrophilic component in the colon and jejunum, respectively.Further studies will investigate time course and tissue differences.The efficacy of AVX-470m in both models highlights the central role of TNF in GI tract inflammation, and supports the therapeutic potential of an oral anti-TNF antibody in GI inflammatory disease.
