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Fistula closure is achieved by using the anal fistula plug in approximately 54% of patients without Crohn's disease. The anal fistula plug has not been adequately evaluated in the Crohn's population.

Purpose: We have reported previously that intratumoral microvessel density (MVD) is a significant prognostic indicator of event-free survival in the Ewing's sarcoma family of tumors (ESFT). Here, the angiogenic growth factor expression profile and its relationship with MVD has been investigated in ESFT. Experimental Design and Results: Using ESFT model systems, the potential of these factors as therapeutic targets has been evaluated. A significant correlation (P = 0.02) was observed between vascular endothelial growth factor (VEGF) expression and MVD, consistent with the hypothesis that VEGF regulates the development of microvessels in ESFT. There was no correlation between MVD and any of the other growth factors studied. All six ESFT cell lines studied produced and secreted VEGF; five of six cell lines also secreted placental growth factor, one cell line (A673) at high levels. Tumor conditioned medium induced proliferation of human umbilical vein endothelial cells. Expression of VEGF receptors Flt-1 and Flk-1/KDR was heterogeneous across the cell lines. Both receptor tyrosine kinase inhibitors SU6668 (targets Flk-1/KDR, platelet-derived growth factor receptor-β, and fibroblast growth factor receptor 1) and SU5416 (targets Flk-1/KDR) as well as anti-VEGF agents rhuMAb-VEGF (bevacizumab) and VEGF Trap delayed s.c. growth of ESFT in mice compared with untreated groups: SU6668 (100 mg/kg/d), SU5416 (25 mg/kg/d), rhuMAb-VEGF (10 mg/kg twice weekly), and VEGF Trap (2.5 or 25 mg/kg twice weekly). Conclusions: These data suggest that VEGF is the single most important regulator of angiogenesis in ESFT and may be exploited for therapeutic advantage.

Purpose:To discover and validate serum glycoprotein biomarkers in ovarian cancer using proteomic-based approaches. Experimental Design: Serum samples from a ''discovery set''of 20 patients with ovarian cancer or benign ovarian cysts or healthy volunteers were compared by fluorescence two-dimensional differential in-gel electrophoresis and parallel lectin-based two-dimensional profiling.Validation of a candidate biomarker was carried out with Western blotting and immunoassay (n = 424). Results: Twenty-six proteins that changed significantly were identified by mass spectrometric sequencing. One of these, confirmed byWestern blotting, was afamin, a vitamin E binding protein, with two isoforms decreasing in patients with ovarian cancer. Validation using cross-sectional samples from 303 individuals (healthy controls and patients with benign, borderline, or malignant ovarian conditions and other cancers) assayed by ELISA showed significantly decreased total afamin concentrations in patients with ovarian cancer compared with healthy controls (P = 0.002) and patients with benign disease (P = 0.046). However, the receiver operating characteristic areas for total afamin for the comparison of ovarian cancer with healthy controls or benign controls were only 0.67 and 0.60, respectively, with comparable figures for CA-125 being 0.92 and 0.88 although corresponding figures for a subgroup of samples analyzed by isoelectric focusing for afamin isoform 2 were 0.85 and 0.79. Analysis of a further 121 samples collected prospectively from 9 patients pretreatment through to relapse indicated complementarity of afamin with CA-125, including two cases in whom CA-125 was noninformative. Conclusions: Afamin shows potential complementarity with CA-125 in longitudinal monitoring of patients with ovarian cancer, justifying prospective larger-scale investigation. Changes in specific isoforms may provide further information.

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ObjectivesTo develop and validate tests to assess the risk of any cancer for patients referred to the NHS Urgent Suspected Cancer (2-week wait, 2WW) clinical pathways.SettingPrimary and secondary care, one participating regional centre.ParticipantsRetrospective analysis of data from 371 799 consecutive 2WW referrals in the Leeds region from 2011 to 2019. The development cohort was composed of 224 669 consecutive patients with an urgent suspected cancer referral in Leeds between January 2011 and December 2016. The diagnostic algorithms developed were then externally validated on a similar consecutive sample of 147 130 patients (between January 2017 and December 2019). All such patients over the age of 18 with a minimum set of blood counts and biochemistry measurements available were included in the cohort.Primary and secondary outcome measuressensitivity, specificity, negative predictive value, positive predictive value, Receiver Operating Characteristic (ROC) curve Area Under Curve (AUC), calibration curvesResultsWe present results for two clinical use-cases. In use-case 1, the algorithms identify 20% of patients who do not have cancer and may not need an urgent 2WW referral. In use-case 2, they identify 90% of cancer cases with a high probability of cancer that could be prioritised for review.ConclusionsCombining a panel of widely available blood markers produces effective blood tests for cancer for NHS 2WW patients. The tests are affordable, and can be deployed rapidly to any NHS pathology laboratory with no additional hardware requirements.