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| 1 | In vivo subsurface morphological and functional cellular and subcellular imaging of the gastrointestinal tract with confocal mini-microscopy显示文摘瞄准:为在活体内评估一根最新发达的手持的共焦的探针在啮齿类动物的完全的胃肠道的显微镜的成像。方法:一根新奇僵硬共焦的探针(直径 7 公里) 为 fluorophore 刺激用 488 nm 单身者线激光在人为使用与类似于灵活 endomicroscopy 系统的光特征被设计。轻排放在 505 ~ 750 nm 被检测。看法的地多样地是 475 妈妈 475 妈妈。光片厚度是有 0.7 妈妈的侧面的分辨率的 7 妈妈。在不同深度(到 250 妈妈的表面) 的表面下的连续图象多样地在 1024 点在实时被产生由在轻轻的、稳定的接触把探查放到织物上的 1024 个象素(0.8 frames/s ) 。织物标本为组织病理学说的关联被取样。结果:食管,胃,小并且大肠和中央,肝,胰和胆囊是在在 n = 的高分辨率的视觉 ised 在活体内 48 个鼠标。有共焦的微型显微镜学探查的实时显微镜的成像是容易的完成。不同染色协议(荧光黄,吖啶黄,标记 FITC 的葡聚糖和 L。可食用嗯植物凝血素) 织物的每个加亮的特定的方面,和在活体内成像与常规组织学最优地相关。在活体内血流监视把功能的质量加到词法成像。结论:共焦的显微镜学是在甚至表面下的织物结构的高分辨率允许完全的官方补给的道的可视化的可行在活体内。在这研究评估的新共焦的探查设计与腹腔镜检查兼容并且显著地扩展可能的应用的地到 intra 腹的机关。它允许新在活体内染色和申请选择的立即的测试因此在病人从动物研究允许快速的转移到临床的使用。 | Martin Goetz Beena Memadathil Stefan Biesterfeld Constantin Schneider Sebastian Gregor Peter R Galle Markus F Neurath Ralf Kiesslich | 2007 | World Journal of Gastroenterology2007，13，15： | 6 |
| 2 | Epigenetics and pancreatic cancer:Pathophysiology and novel treatment aspects显示文摘An improvement in pancreatic cancer treatment represents an urgent medical goal.Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades.Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations,such as mutations of K-ras,and especially epigenetic dysregulation of tumor-associated genes,such as silencing of the tumor suppressor p16ink4a,are hallmarks of pancreatic cancer.Here,we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation,histone acetylation or miRNA(microRNA)expression,and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition,morphological pattern formation,or cancer stem cell regulation during carcinogenesis from PanIN(pancreatic intraepithelial lesions)to invasive cancer and resistance development.Epigenetic drugs,such as DNA methyltransferases or histone deactylase inhibitors,have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development.Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients. | Daniel Neureiter Tarkan Jger Matthias Ocker Tobias Kiesslich | 2014 | World Journal of Gastroenterology2014，20，24： | 6 |
| 3 | Differential role of Hedgehog signaling in human pancreatic(patho-)physiology:An up to date review显示文摘Since the discovery of the Hedgehog(Hh)pathway in drosophila melanogaster,our knowledge of the role of Hh in embryonic development,inflammation,and cancerogenesis in humans has dramatically increased over the last decades.This is the case especially concerning the pancreas,however,real therapeutic breakthroughs are missing until now.In general,Hh signaling is essential for pancreatic organogenesis,development,and tissue maturation.In the case of acute pancreatitis,Hh has a protective role,whereas in chronic pancreatitis,Hh interacts with pancreatic stellate cells,leading to destructive parenchym fibrosis and atrophy,as well as to irregular tissue remodeling with potency of initiating cancerogenesis.In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment.The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials(phases 1 and 2).Furthermore,a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach.In this review,we give a structured survey of the role of the Hh pathway in pancreatic development,pancreatitis,pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer. | Eckhard Klieser Stefan Swierczynski Christian Mayr Tarkan Jager Johanna Schmidt Daniel Neureiter Tobias Kiesslich Romana Illig | 2016 | World Journal of Gastrointestinal Pathophysiology2016，7，2： | 5 |
| 4 | Hepatocellular carcinoma: Therapeutic advances in signaling,epigenetic and immune targets显示文摘Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besides first and second generation tyrosine kinase inhibitors,immune checkpoint inhibitors have become central for the treatment of HCC.New modalities like epigenetic therapy using histone deacetylase inhibitors(HDACi)and cell therapy approaches with chimeric antigen receptor T cells(CAR-T cells)are currently under investigation in clinical trials.Development of such novel drugs is closely linked to the availability and improvement of novel preclinical and animal models and the identification of predictive biomarkers.The current status of treatment options for advanced HCC,emerging novel therapeutic approaches and different preclinical models for HCC drug discovery and development are reviewed here. | Daniel Neureiter Sebastian Stintzing Tobias Kiesslich Matthias Ocker | 2019 | World Journal of Gastroenterology2019，25，25： | 4 |
| 5 | How to establish endoscopic submucosal dissection in Western countries显示文摘Endoscopic submucosal dissection(ESD) has been invented in Japan to provide resection for cure of early cancer in the gastrointestinal tract. Professional level of ESD requires excellent staging of early neoplasias with image enhanced endoscopy(IEE) to make correct indications for ESD,and high skills in endoscopic electrosurgical dissection. In Japan,endodiagnostic and endosurgical excellence spread through personal tutoring of skilled endoscopists by the inventors and experts in IEE and ESD. To translocate this expertise to other continents must overcome two fundamental obstacles:(1) inadequate expectations as to the complexity of IEE and ESD; and(2) lack of suitable lesions and master-mentors for ESD trainees. Leading endoscopic mucosal resection-proficient endoscopists must pioneer themselves through the long learning curve to proficient ESD experts. Major referral centers for ESD must arise in Western countries on comparable professional level as in Japan. In the second stage,the upcoming Western experts must commit themselves to teach skilled endoscopists from other referral centers,in order to spread ESD in Western countries. Respect for patients with early gastrointestinal cancer asks for best efforts to learn endoscopic categorization of early neoplasias and skills for ESD based on sustained cooperation with the masters in Japan. The strategy is discussed here. | Tsuneo Oyama Naohisa Yahagi Thierry Ponchon Tobias Kiesslich Frieder Berr | 2015 | World Journal of Gastroenterology2015，21，40： | 3 |
| 6 | 在每日的内视镜检查法常规挑选操作员 choledochoscopy 和它的角色显示文摘 Different diagnostic procedures exist for the detection of bile duct lesions in clinical practice.However,neither retrograde contrast imaging of the bile duct endoscopic retrograde cholangiopancreatogram nor other imaging procedures allow a safe diagnosis of the lesions.Therefore choledochoscopy may be a useful diagnostic procedure in macroscopic assessing lesions of the bile duct.Even if the diagnostic sensitivity and specificity is not sufficient,first studies suggest an enhanced diagnostic accuracy for choledochoscopy.Since the progress of choledochoscopy has started in the 1970 different improvements were achieved.Meanwhile,the examination can be performed by an examiner and samples can be taken.Image and Resolution quality has improved over the past years,also.The SpyGlass system is a technically advanced cholangioscopic device to provide endoscopic diagnosis in case of inconclusive bile duct findings.Further more,two more lumina allow specific biopsy forceps and optical fibers for electrohydraulic or laser lithotripsy.The most frequent useful insert of SpyGlass in clinical practice are in complex gallstones and bile duct lesions of unclear dignity. | Arthur Hoffman Johannes Wilhelm Rey Ralf Kiesslich | 2013 | World Journal of Gastrointestinal Endoscopy2013，5，5： | 3 |
| 7 | Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo显示文摘 | Ralf Kiesslich Juergen Burg Michael Vieth Janina Gnaendiger Meike Enders Peter Delaney Adrian Polglase Wendy McLaren Daniela Janell Steven Thomas Bernhard Nafe Peter R. Galle Markus F. Neurath | 2004 | Gastroenterology2004，，3： | 3 |
| 8 | International Consensus Statement on surveillance and management of dysplasia in inflammatory bowel disease显示文摘 | Loren Laine Tonya Kaltenbach Alan Barkun Kenneth R. McQuaid Venkataraman Subramanian Roy Soetikno James E. East Francis A. Farraye Brian Feagan John Ioannidis Ralf Kiesslich Michael Krier Takayuki Matsumoto Robert P. McCabe Klaus M?nkemüller Robert Odze M | 2014 | Gastrointestinal Endoscopy2014，，： | 3 |
| 9 | Feasibility of confocal endomicroscopy in the diagnosis of pediatric gastrointestinal disorders显示文摘AIM:To evaluate the feasibility and utility of confocal laser endomicroscopy(CLE) in the description of normal gastrointestinal(GI) mucosa and in the diagnosis of GI disorders in children,in comparison to histology.METHODS:Forty-four patients(19 female) median age 10.9 years(range 0.7-16.6 years) with suspected or known GI pathology underwent esophago-gastro-duodenoscopy(OGD)(n = 36) and/or ileocolonoscopy(IC)(n = 31) with CLE using sodium fluorescein and acriflavine as contrast agents.Histological sections were compared with same site confocal images by two experienced pediatric and GI histopathologists and endoscopists,respectively.RESULTS:Duodenum and ileum were intubated in all but one patient undergoing OGD and IC.The median procedure time was 16.4 min(range 7-25 min) for OGD and 27.9 min(range 15-45 min) for IC.A total of 4798 confocal images were compared with 153 biopsies from the upper GI tract from 36 procedures,and 4661 confocal images were compared with 188 biopsies from the ileocolon from 31 procedures.Confocal images were comparable to conventional histology both in normal and in pathological conditions such as esophagitis,Helicobacter pylori gastritis,celiac disease,inflammatory bowel disease,colonic heterotopia,and graft versus host disease.CONCLUSION:CLE offers the prospect of targeting biopsies to abnormal mucosa,thereby increasing diagnostic yield,reducing the number of biopsies,decreasing the burden on the histopathological services,and reducing costs. | Krishnappa Venkatesh Marta Cohen Clair Evans Peter Delaney Steven Thomas Christopher Taylor Ashraf Abou-Taleb Ralf Kiesslich Mike Thomson | 2009 | World Journal of Gastroenterology2009，15，18： | 2 |
| 10 | Advanced colonoscopic imaging using endocytoscopy显示文摘 | Helmut Neumann Shin‐Ei Kudo Ralf Kiesslich Markus F. Neurath | 2015 | Digestive Endoscopy2015，，2： | 2 |
| 11 | Confocal laser endomicroscopy for the differential diagnosis of ulcerative colitis and Crohn’s disease: a pilot study显示文摘 | Gian Tontini Jonas Mudter Michael Vieth Raja Atreya Claudia Günther Yurdagül Zopf Dane Wildner Ralf Kiesslich Maurizio Vecchi Markus Neurath Helmut Neumann | 2014 | Endoscopy2014，，： | 2 |
| 12 | Efficacy of SpyGlass^(TM)-directed biopsy compared to brush cytology in obtaining adequate tissue for diagnosis in patients with biliary strictures显示文摘AIM: To evaluate the diagnostic yield(inflammatory activity) and efficiency(size of the biopsy specimen) of SpyGlassTM-guided biopsy vs standard brush cytology in patients with and without primary sclerosing cholangitis(PSC).METHODS: At the University Medical Center Mainz, Germany, 35 consecutive patients with unclear biliarylesions(16 patients) or long-standing PSC(19 patients) were screened for the study. All patients underwent a physical examination, lab analyses, and abdominal ultrasound. Thirty-one patients with non-PSC strictures or with PSC were scheduled to undergo endoscopic retrograde cholangiography(ERC) and subsequent per-oral cholangioscopy(POC). Standard ERC was initially performed, and any lesions or strictures were localized. POC was performed later during the same session. The Boston Scientific SpyGlass SystemTM(Natick, MA, United States) was used for choledochoscopy. The biliary tree was visualized, and suspected lesions or strictures were biopsied, followed by brush cytology of the same area. The study endpoints(for both techniques) were the degree of inflammation, tissue specimen size, and the patient populations(PSC vs non-PSC). Inflammatory changes were divided into three categories: none, low activity, and high activity. The specimen quantity was rated as low, moderate, or sufficient.RESULTS: SpyGlassTM imaging and brush cytology with material retrieval were performed in 29 of 31(93.5%) patients(23 of the 29 patients were male). The median patient age was 45 years(min, 20 years; max, 76 years). Nineteen patients had known PSC, and 10 showed non-PSC strictures. No procedure-related complications were encountered. However, for both methods, tissues could only be retrieved from 29 pa-tients. In cases of inflammation of the biliary tract, the diagnostic yield of the SpyGlassTM-directed biopsies was greater than that using brush cytology. More tissue material was obtained for the biopsy method than for the brush cytology method(P = 0.021). The biopsies showed significantly more inflammatory characteristics and greater inflammatory activity compared to the cy-tological investigation(P = 0.014). The greater quantity of tissue samples proved useful for both PSC and non-PSC patients.CONCLUSION: SpyGlassTM imaging can be recom-mended for proper inflammatory diagnosis in PSC pa-tients. However, its value in diagnosing dysplasia wasnot addressed in this study and requires further investi-gation. | Johannes Wilhelm Rey Torsten Hansen Sebastian Dümcke Achim Tresch Katja Kramer Peter Robert Galle Martin Goetz Marcus Schuchmann Ralf Kiesslich Arthur Hoffman | 2014 | World Journal of Gastrointestinal Endoscopy2014，6，4： | 2 |
| 13 | Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis显示文摘 | Ralf Kiesslich Johannes Fritsch Martin Holtmann Heinz H. Koehler Manfred Stolte Stephan Kanzler Bernhard Nafe Michael Jung Peter R. Galle Markus F. Neurath | 2003 | Gastroenterology2003，，4： | 2 |
| 14 | In vivo molecular imaging with cetuximab, an anti-EGFR antibody, for prediction of response in xenograft models of human colorectal cancer显示文摘 | M. Goetz M. Hoetker M. Diken P. Galle R. Kiesslich | 2013 | Endoscopy2013，，： | 2 |
| 15 | Chromoscopy-Guided Endomicroscopy Increases the Diagnostic Yield of Intraepithelial Neoplasia in Ulcerative Colitis显示文摘 | Ralf Kiesslich Martin Goetz Katharina Lammersdorf Constantin Schneider Juergen Burg Manfred Stolte Michael Vieth Bernhard Nafe Peter R. Galle Markus F. Neurath | 2007 | Gastroenterology2007，，3： | 2 |
| 16 | GERD—Barrett—Adenocarcinoma: Do We Have Suitable Prognostic and Predictive Molecular Markers?显示文摘 | Romana Illig Eckhard Klieser Tobias Kiesslich Daniel Neureiter P. Marco Fisichella | 2013 | Gastroenterology Research and Practice2013，，： | 2 |
| 17 | Recognition and characterization of small colonic neoplasia with high-definition colonoscopy using i-Scan is as precise as chromoendoscopy显示文摘 | A. Hoffman C. Kagel M. Goetz A. Tresch J. Mudter S. Biesterfeld P.R. Galle M.F. Neurath R. Kiesslich | 2009 | Digestive and Liver Disease2009，，1： | 2 |
| 18 | Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo 显示文摘 | Kiesslich R Burg J Vieth M | 2004 | Gastroenterology2004，127，： | 1 |
| 19 | Apoptosis following photodynamic tumor therapy:induction,mechanisms and detection显示文摘 | Plaetzer K Kiesslich T Oberdanner CB | 2005 | Curr Pharm Des2005，11，9： | 1 |
| 20 | Recognition and characterization of small colonic neoplasia with high-definition colonoscopy using i-Scan is as precise as chromoendoscopy显示文摘 | A. Hoffman C. Kagel M. Goetz A. Tresch J. Mudter S. Biesterfeld P.R. Galle M.F. Neurath R. Kiesslich | 2009 | Digestive and Liver Disease2009，，1： | 1 |
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