Patients with Crohn’s disease commonly develop ileal and less commonly colonic strictures, containing various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment, predominantly fibrotic strictures currently require endoscopic balloon dilation or surgery. Therefore, differentiation of the main components of a stricturing lesion is key for defining the therapeutic management. The role of endoscopy to diagnose the nature of strictures is limited by the superficial inspection of the intestinal mucosa, the lack of depth of mucosal biopsies and by the risk of sampling error due to a heterogeneous distribution of inflammation and fibrosis within a stricturing lesion. These limitations may be in part overcome by cross-sectional imaging techniques such as ultrasound, CT and MRI, allowing for a full thickness evaluation of the bowel wall and associated abnormalities. This systematic literature review provides a comprehensive summary of currently used radiologic definitions of strictures. It discusses, by assessing only manuscripts with histopathology as a gold standard, the accuracy for diagnosis of the respective modalities as well as their capability to characterise strictures in terms of inflammation and fibrosis. Definitions for strictures on cross-sectional imaging are heterogeneous; however, accuracy for stricture diagnosis is very high. Although conventional cross-sectional imaging techniques have been reported to distinguish inflammation from fibrosis and grade their severity, they are not sufficiently accurate for use in routine clinical practice. Finally, we present recent consensus recommendations and highlight experimental techniques that may overcome the limitations of current technologies.

Boras et al. demonstrate that Skap2, via interaction with WASp, regulates actin polymerization and binding of talin-1 and kindlin-3 to the β2 integrin, thereby being indispensable for β2 integrin activation and neutrophil recruitment.

The life expectancy of unresectable hilar cholangiocellular carcinomas (CCCs) is very limited and endoscopic radiofrequency ablation (ERFA) of the biliary tract may prolong survival. Our single-center-study retrospectively analysed all CCC cases, in whom ERFAs of the biliary tract were performed between 2012 and 2017 and compared these to historical control cases who received the standard treatment of sole stent application. ERFA was performed in 32 patients with malignant biliary strictures that were mainly caused by Bismuth III and IV hilar CCCs (66%). 14 of these patients received repeated ERFAs, for an overall performance of 54 ERFAs. Stents were applied after examination of all patients (100%). Adverse events occurred in 18.5% of examinations. Case-control analysis revealed that the survival time of cases with unresectable Bismuth type III and IV hilar CCCs (n = 20) treated with combined ERFA and stent application significantly increased compared to controls (n = 22) treated with sole stent application (342 +/− 57 vs. 221 +/− 26 days; p = 0.046). In conclusion, ERFA therapy significantly prolonged survival in patients with unresectable Bismuth type III and IV hilar CCC. As an effective and safe method, ERFA should be considered as a palliative treatment for all these patients.

Background: Digital single-operator cholangioscopes (digital SOCs), equipped with an improved image quality, have been recently introduced. Objective: The aim of this study is to evaluate the safety and diagnostic and therapeutic efficacy of digital SOCs (Spyglass TM DS). Methods: Sixty-seven digital SOC procedures performed between 2015 and 2017 were retrospectively analyzed. Results: The most frequent indications for examination were indeterminate biliary strictures (61.2%) and biliary stone disease (23.9%). In 25 patients (37.3), visual findings predicted malignancy with a sensitivity of 88.9%, a specificity of 97.6%, a positive predictive value (PPV) of 96.0% and a negative predictive value (NPV) of 92.9%. For histological analysis, forceps biopsies were performed in 29 patients (43.2%). Compared with visual findings, forceps biopsies yield a lower diagnostic efficacy in diagnosing malignancy (sensitivity 62.5%, specificity 90.0%, PPV 90.9%, NPV 60.0%). Therapeutic interventions were performed in 19 patients with a technical success rate of 89.4%. Adverse events were observed in 17 patients (25.4%). Of these, 11 patients (16.4%) suffered from severe adverse events (pancreatitis, cholangitis or major bleeding), which led to a prolonged hospital stay. Conclusion: Digital SOCs have excellent diagnostic and therapeutic efficacies, but are accompanied by high rates of adverse events; therefore, physicians should use digital SOCs in carefully selected cases. KeywordsCholangioscopy, SpyGlass DS, adverse events, digital single-operator cholangioscopy, indeterminate biliary strictures, complex biliary stone disease Received: 25 November 2017; accepted: 12 February 2018 Key summaryEstablished knowledge:. Digital single-operator cholangioscopes (digital SOCs) have been recently introduced. New findings:. Digital SOCs have an excellent diagnostic accuracy for biliary tract diseases and a high efficacy for therapeutic interventions including treatment of complex biliary stone disease and biliary strictures. . Our results suggest a high incidence (16.4%) of severe adverse events associated with the examination, which is why digital SOCs should only be used in carefully selected cases.

SummaryBackgroundEvidence for endoscopic balloon dilation of small intestinal strictures in Crohn's disease (CD) using balloon‐assisted enteroscopy is scarce.AimTo evaluate endoscopic balloon dilation for the treatment of small intestinal CD strictures using balloon‐assisted enteroscopy.MethodsCitations in Embase, MEDLINE, and Cochrane were systematically reviewed. In a meta‐analysis of 18 studies with 463 patients and 1189 endoscopic balloon dilations, technical success was defined as the ability to dilate a stricture. Individual data were also obtained on 218 patients to identify outcome‐relevant risk factors.ResultsIn the pooled per‐study analysis, technical success rate of endoscopic balloon dilation was 94.9%, resulting in short‐term clinical efficacy in 82.3% of patients. Major complications occurred in 5.3% of patients. During follow‐up, 48.3% of patients reported symptom recurrence, 38.8% were re‐dilated and 27.4% proceeded to surgery. On the per‐patient‐based multivariable analysis, that patients with disease activity in the small intestine had lower short‐term clinical efficacy (odds ratio 0.32; 95% confidence interval 0.14‐0.73, P = 0.007). Patients with concomitant active disease in the small and/or large intestine had an increased risk to proceed toward surgery (hazard ratio 1.85; 95% confidence interval 1.09‐3.13, P = 0.02 and hazard ratio 1.77; 95% confidence interval 1.34‐2.34, P < 0.001).ConclusionsBalloon‐assisted enteroscopy for dilatation of CD‐associated small intestinal strictures has high short‐term technical and clinical efficacy and low complication rates. However, up to two‐thirds of patients need re‐dilation or surgery.

© F e r r a t a S t o r t i F o u n d a t i o nations are most likely required for ETV6/RUNX1-positive leukemogenesis and might be important for the differences in clinical outcome. More than 80% of initial ETV6/RUNX1-positive ALL display additional genetic alterations of the ETV6 and RUNX1 gene loci in fluorescence in situ hybridization (FISH) analyses. These include deletions of the untranslocated ETV6 gene (70%), an extra copy of RUNX1 (23%) and duplication of the derivative chromosome der(21) t(12;21) (10%). 18 At relapse, additional alterations of chromosomes 12 and 21 are often detected in leukemic cells as well (85%). 19 Current genome wide high resolution analyses of DNA copy number alterations (CNA) have identified numerous genetic alterations in childhood ALL. [20][21][22][23] In initial ETV6/RUNX1-positive ALL, genes related to B-lymphocyte development and differentiation, cell cycle regulation, tumor suppression and apoptosis are recurrently affected. 20,21,[24][25][26][27] Recent DNA copy number analyses on matched initial diagnosis and relapse ALL samples revealed that CNA acquired at relapse primarily affect genes implicated in cell cycle regulation, B-cell development, drug metabolism and drug response. 25,28,29 In the present study, leukemic cell DNA from 51 patients with a first relapse of ETV6/RUNX1-positive ALL enrolled in and treated according to the ALL-REZ BFM relapse trials were examined by whole genome array comparative genomic hybridization (CGH) for cooperating genetic lesions. This cohort represents the largest number of patients analyzed so far, enabling the investigation of an association between identified CNA and relapse-specific clinical and prognostic parameters for the first time. Methods Patients and samplesLeukemic bone marrow samples from 51 patients with first relapse of an ETV6/RUNX1-positive BCP-ALL were collected at relapse diagnosis after written informed consent was obtained from the patients, their parents or guardians in accordance with the ethical committee of the Charité and the declaration of Helsinki. All patients were enrolled in and treated according to ALL-REZ relapse trials 90, 95/96, and 2002 of the BFM study group, which were approved by the Institutional Review Boards of the Charité and the FU-Berlin, Germany. Diagnostic bone marrow samples were selected to contain >60% leukemic cells prior to further enrichment by Ficoll-density gradient separation of mononuclear cells. The presence of the ETV6/RUNX1 fusion was detected by reverse transcriptase polymerase chain reaction analysis as described previously. 9 DNA isolationLeukemic cell samples were prepared and DNA isolated from bone marrow or peripheral blood mononuclear cells of all patients and of 20 healthy controls, serving as gender-specific control DNA, as described previously. 30 All DNA samples were amplified using the GenomePlex Whole Genome Amplification Kit (SigmaAldrich Chemie GmbH, Munich, Germany) following the manufacturer's directions. Array comparative genomic hybridizationArray CGH...

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Digital SOC-assisted guidewire placements have high technical success rates, especially in benign biliary strictures. This technique can help to avoid more invasive procedures such as percutaneous transhepatic or endoscopic ultrasound-guided biliary drainage.