Extracellular matrix metalloproteinase inducer (EMMPRIN) is a potential biomarker of angiogenesis in proliferative diabetic retinopathy.

PURPOSE: Extracellular matrix metalloproteinase inducer (EMMPRIN) promotes angiogenesis through matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) production. We investigated the expression levels of EMMPRIN and correlated these levels with VEGF, MMP-1 and MMP-9 in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of EMMPRIN in the retinas of diabetic rats and the effect of EMMPRIN on the induction of angiogenesis regulatory factors in human retinal microvascular endothelial cells (HRMECs). METHODS: Vitreous samples from 40 PDR and 19 non-diabetic patients, epiretinal membranes from 12 patients with PDR, retinas of rats and HRMECs were studied by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, Western blot analysis, zymography analysis and RT-PCR. RESULTS: We showed a significant increase in the expression of EMMPRIN, VEGF, MMP-1 and MMP-9 in vitreous samples from PDR patients compared with non-diabetic controls (p < 0.0001; p = 0.001; p = 0.009; p < 0.0001, respectively). Significant positive correlations were found between the levels of EMMPRIN and the levels of VEGF (r = 0.38; p = 0.003), MMP-1 (r = 0.36; p = 0.005) and MMP-9 (r = 0.46; p = 0.003). In epiretinal membranes, EMMPRIN was expressed in vascular endothelial cells and stromal cells. Significant increase of EMMPRIN mRNA was detected in rat retinas after induction of diabetes. EMMPRIN induced hypoxia-inducible factor-1α, VEGF and MMP-1 expression in HRMEC. CONCLUSIONS: These results suggest that EMMPRIN/MMPs/VEGF pathway is involved in PDR angiogenesis.

Results of the Fifth Scientific Workshop of the ECCO [II]: Clinical Aspects of Perianal Fistulising Crohn's Disease-the Unmet Needs.

BACKGROUND AND AIMS: Perianal fistulas affect up to one-third of Crohn's patients during the course of their disease. Despite the considerable disease burden, current treatment options remain unsatisfactory. The Fifth Scientific Workshop [SWS5] of the European Crohn's and Colitis Organisation [ECCO] focused on the pathophysiology and clinical impact of fistulas in the disease course of patients with Crohn's disease [CD]. METHODS: The ECCO SWS5 Working Group on clinical aspects of perianal fistulising Crohn's disease [pCD] consisted of 13 participants, gastroenterologists, colorectal surgeons, and a histopathologist, with expertise in the field of inflammatory bowel diseases. A systematic review of literature was performed. RESULTS: Four main areas of interest were identified: natural history of pCD, morphological description of fistula tracts, outcome measures [including clinical and patient-reported outcome measures, as well as magnetic resonance imaging] and randomised controlled trials on pCD. CONCLUSIONS: The treatment of perianal fistulising Crohn's disease remains a multidisciplinary challenge. To optimise management, a reliable classification and proper trial endpoints are needed. This could lead to standardised diagnosis, treatment, and follow-up of Crohn's perianal fistulas and the execution of well-designed trials that provide clear answers. The prevalence and the natural history of pCD need further evaluation.

Decreased lymphatic vessel density is associated with postoperative endoscopic recurrence in Crohn's disease.

BACKGROUND: Increased lymphatic vessel (LV) density has been found in uninflamed intestinal wall of patients with Crohn's disease (CD). The goal of the study was to search for an association between LV density in the proximal ileal resection margin at the time of surgery and endoscopic recurrence. METHODS: Ileocolonic resection specimens were obtained from 28 CD patients and 10 control subjects. The ileal proximal uninflamed section was used for the histological quantification of LV using immunohistochemistry with D2-40 antibody in the mucosa and submucosa. Quantification of LV was performed in 8 consecutive fields and was blinded to recurrence score. Patients were divided into 2 groups based on the presence (Rutgeerts score, i3/i4) (R+) or absence (Rutgeerts score, i0/i1) (R-) of endoscopic recurrence 1 year after the surgery. All patients were free of immunomodulators or biologics between surgery and postoperative endoscopy. RESULTS: Median LV density was lower in control subjects than in CD patients in the mucosa (4.5%; interquartile range [IQR], 3.6-5.3 versus 5.9%; IQR, 4.2-8.5; P = 0.04) and submucosa (2.4%; IQR, 1.9-3.6 versus 5.7%; IQR, 4.3-6.9; P < 0.01). R- patients had a higher LV density in the proximal resection margin at surgery than R+ patients, both in the mucosa (8.5%; IQR, 6.5-10.3 versus 4.4%; IQR, 3.1-6.1; P < 0.01) and in the submucosa (6.3%; IQR, 5.5-9.3 versus 5.3%; IQR, 3.4-5.9; P = 0.03). Mucosal LV density greater than 7% predicted the absence of endoscopic recurrence at 1 year, with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Decreased LV density is associated with high risk of endoscopic recurrence after surgery. Therapies that improve lymphatic flow in the gut may reduce the incidence of endoscopic recurrence.

T(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas are heterogeneous with respect to the V(H) gene mutation status.

AIM: To investigate how t(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas relate to other marginal zone lymphomas with respect to the somatic mutation pattern of the V(H) genes and the expression of the marker CD27. METHODS: The V(H) gene of 7 t(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas was amplified by PCR using family specific V(H) primers and a consensus J(H) primer. PCR products were sequenced and mutation analysis of the CDR and the FR regions was performed. All cases were immunostained for CD27. RESULTS: One case showed unmutated V(H) genes while the others showed mutated V(H) genes with mutation frequencies ranging from 1.3 to 14.7% and with evidence of antigen selection in 2 cases. These data suggest that the translocation t(11;18)(q21;q21) can target either B-cells at different stages of differentiation or naive B-cells that retain the capacity to differentiate upon antigen stimulation. All cases but one displayed weak to strong CD27 expression which did not correlate with the V(H) gene mutation status. CONCLUSION: t(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas are heterogeneous with respect to the V(H) mutation status and CD27 is not a marker of somatically mutated B-cells.