Advanced gastrointestinal endoscopic imaging forinflammatory bowel diseases

Gastrointestinal luminal endoscopy is of paramount importance for diagnosis, monitoring and dysplasia surveillance in patients with both, Crohn's disease and ulcerative colitis. Moreover, with the recent recognition that mucosal healing is directly linked to the clinical outcome of patients with inflammatory bowel disorders, a growing demand exists for the precise, timely and detailed endoscopic assessment of superficial mucosal layer. Further, the novel field of molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy, now encompassing not only diagnosis, surveillance, and treatment but also the prediction of individual therapeutic responses. Within this review, we describe how novel endoscopic approaches and advanced endoscopic imaging methods such as high definition and high magnification endoscopy, dye-based and dye-less chromoendoscopy, confocal laser endomicroscopy, endocytoscopy and molecular imaging now allow for the precise and ultrastructural assessment of mucosal inflammation and describe the potential of these techniques for dysplasia detection.

Innovative immunohistochemistry identifies MMP-9 expressing macrophages at the invasive front of murine HCC

AIM:To investigate the proteolytic contribution of tumor-associated macrophages(TAM)in tumor invasion,we analyzed whether TAM at the invasive front of small HCC in Abcb4-/--mice show an enhanced expression of MMP-9. METHODS:Liver cryosections of the hepatocellular carcinoma(HCC)invasive front from 12 mo old Abcb4-/--mice were stained for collagen typeⅠand MMP-9 using Alexa488 and Alexa568 labeled secondary antibodies.Afterwards,the Alexa568 dye was bleached and the macrophage marker F4/80 was visualized using Alexa568 labeled secondary antibodies.Finally, photographs of the invasive tumor front were digitally overlaid and analyzed. RESULTS:After complete bleaching of the primary dye,specific fluorescence staining of a third antigen, here F4/80,was successfully performed on the same histological section.With this method,we were able to identify conglomerates of matrix metalloproteinase (MMP-9)expressing macrophages within the tumor capsule of HCC. CONCLUSION:MMP-9 expressing macrophages are involved in matrix remodelling at the invasive tumor front of HCC.The described staining protocol provides a simple yet powerful extension of conventional immuno-histochemistry,facilitating visualization of at least three different antigens plus nuclei in one single histological section.

First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy

We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.

Comparison of Hemospray~? and Endoclot? for the treatment of gastrointestinal bleeding

BACKGROUND Gastrointestinal(GI) bleeding is a common indication for endoscopy. For refractory cases, hemostatic powders(HP) represent "touch-free" agents.AIM To analyze short term(ST-within 72 h-) and long-term(LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray(HS) and Endoclot(EC).METHODS HP was applied in 154 consecutive patients(mean age 67 years) with GI bleeding.Patients were followed up for 1 mo(mean follow-up: 3.2 mo).RESULTS Majority of applications were in upper GI tract(89%) with following bleeding sources: peptic ulcer disease(35%), esophageal varices(7%), tumor bleeding(11.7%), reflux esophagitis(8.7%), diffuse bleeding and erosions(15.3%). Overall ST success was achieved in 125 patients(81%) and LT success in 81 patients(67%). Re-bleeding occurred in 27% of all patients. In 72 patients(47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and64%, with re-bleeding in 32%. As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22%. HS was more frequently applied for upper GI bleeding(P = 0.04)CONCLUSION Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding.

Retrograde inspection vs standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial

BACKGROUND The adenoma detection rate(ADR)is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening colonoscopy.However,adenoma miss rates reach up to 26%and studies have shown that a second inspection of the right colon in retroflected view(RFV)can increase ADR.AIM To assess whether inspection of the whole colon in RFV compared to standard forward view(SFV)can increase ADR.METHODS Patients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two arms.In RFV arm colonoscopy was initially performed with SFV,followed by a second inspection of the whole colon in RFV.In the SFV arm first withdrawal was performed with SFV,followed by a second inspection of the whole colon again with SFV.Number,size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate containers.RESULTS Two hundred and five patients were randomly assigned to the RFV(n=101)and SFV(n=104)arm.In the RFV arm,both polyp detection rate(PDR)and ADR were increased under second inspection in RFV(PDR 1st SFV:39.8%,PDR 2nd RFV:46.6%;ADR 1st SFV:35.2%,ADR 2nd RFV:42%).Likewise,in the SFV arm,PDR and ADR were increased under second inspection(PDR 1st SFV:37.5%,PDR 2nd SFV:46.6%;ADR 1st SFV:34.1%,ADR 2nd SFV:44.3%)with no significant differences in ADR and PDR between the SFV and RFV arm.Mean number of adenomas per patient(APP)was increased in the RFV and SFV(APP RFV arm:1st SFV:1.71;2nd RFV:2.38;APP SFV arm:1st SFV:1.83,2nd SFV:2.2).The majority of adenomas additionally found during second inspection in RFV or in SFV were located in the transverse and left-sided colon and were>5 mm in size.CONCLUSION Second inspection of the whole colon leads to increased adenoma detection with no differences between SFV and RFV.Hence,increased detection is most likely a feature of the second inspection itself but not of the inspection mode.

From the surface to the single cell: Novel endoscopic approaches in inflammatory bowel disease

Inflammatory bowel diseases(IBD) comprise the two major entities Crohn's disease and ulcerative colitis and endoscopic imaging of the gastrointestinal tract has always been an integral and central part in the management of IBD patients. Within the recent years,mucosal healing emerged as a key treatment goal in IBD that substantially decides about the clinical outcome of IBD patients,thereby demanding for a precise,timely and detailed endoscopic assessment of the mucosal inflammation associated with IBD. Further,molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy,now encompassing not only diagnosis,surveillance,and treatment but also the prediction of individual therapy response. Within this review we describe novel endoscopic approaches and advanced endoscopic imaging methods for the diagnosis,treatment and surveillance of IBD patients. We begin by providing an overview over novel and advanced imaging techniques such as magnification endoscopy and dye-based and dye-less chromoendoscopy,endomicroscopy and endocytoscopy. We then describe how these techniques can be utilized for the precise and ultrastructural assessment of mucosal inflammation and dysplasia development associated with IBD and outline how they have enabled the endoscopist to gain insight onto the cellular level in real-time. Finally,we provide an outlook on how molecular imaging has rapidly evolved in the recent past and can be used to make individual predictions about the therapeutic response towards biological treatment.