Ulcerative Colitis: Kiesslich R

Kiesslich R, Goetz M, Neurath MF. · I. Med. Department, Johannes Gutenberg University of Mainz, Germany. · Best Pract Res Clin Gastroenterol. · Pubmed #18790437 No free full text.

Abstract: Confocal laser endomicroscopy enables in vivo microscopy of the mucosal layer of the GI-tract with subcellular resolution during ongoing endoscopy. Endomicroscopy opens a new door for immediate tissue and vessel analysis. Different types of diseases can be diagnosed with optical surface and subsurface analysis. Analysis of the in vivo microarchitecture can be used for targeting biopsies to relevant areas. Furthermore, subsurface imaging can unmask microscopic diseases - (microscopic colitis) or bacterial infection (Helicobacter pylori), for example. Molecular imaging is becoming feasible, and this will shortly open the door to new indications in gastrointestinal endoscopy. This chapter reviews the currently rapidly expanding clinical data about endomicroscopy and gives a look into future research.

Goetz M, Kiesslich R. · First Med Clinic, Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. · Anticancer Res. · Pubmed #18383869 No free full text.

Abstract: Confocal endomicroscopy is a novel technology which allows subsurface histological diagnosis at a cellular and subcellular level in vivo. It thereby provides instantaneous histopathology during ongoing upper and lower endoscopy. This allows immediate diagnosis of neoplastic and inflammatory lesions of the intestinal mucosa. Studies have demonstrated the power of confocal endomicroscopy in screening and surveillance colonoscopy, ulcerative colitis, Barrett's esophagus, and gastric cancer. In animal models of human diseases, the same technology has provided molecular imaging of cancer, functional imaging of altered perfusion in malignant and inflammatory disease and high resolution in vivo morphological diagnosis. Fields of ongoing research are the development of molecular markers for in vivo immunohistochemistry and the application of confocal microscopy to intraabdominal organs in humans. Confocal endomicroscopy is evolving as a novel technique for rapid intravital diagnosis of gastrointestinal neoplastic diseases at the microscopic level and bears the potential for molecular imaging in humans in the future.

Kiesslich R, Goetz M, Vieth M, Galle PR, Neurath MF. · I Med. Klinik und Poliklinik, Johannes Gutenberg Universität Mainz, Mainz, Germany. · Nat Clin Pract Oncol. · Pubmed #17657253 No free full text.

Abstract: Recent studies on a novel technology, denoted confocal laser endomicroscopy (CLE), have altered thinking about the possibilities of endoscopy in the diagnosis and treatment of colorectal cancer. CLE is a new endoscopic tool that allows in vivo histology at subcellular resolution during ongoing endoscopy, and permits subsurface imaging of normal and neoplastic human mucosa. This new technique has unequivocal major implications for the diagnosis and clinical management of patients scheduled for screening or surveillance colonoscopy for colorectal cancer. For instance, CLE allows immediate diagnosis of colonic neoplasias, and the detection of neoplastic cells helps to target endoscopic intervention to relevant areas. Furthermore, the combination of chromoendoscopy with CLE significantly decreases the number of biopsies required for cancer surveillance in patients with ulcerative colitis, but provides a fourfold higher diagnostic yield compared with white-light endoscopy used with random biopsies. Taken together, CLE has led colorectal cancer endoscopy into a new era. CLE can no longer be regarded as just another endoscopic technique, but emerges as a crucial novel imaging technique for in vivo diagnosis of colorectal cancer.

Kiesslich R, Neurath MF. · I. Med. Klinik und Poliklinik, Johannes Gutenberg Universität Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. · Gastroenterol Clin North Am. · Pubmed #16952743 No free full text.

Abstract: The newly developed high-resolution and magnification endoscopes offer features that allow more and new mucosal details to be seen. They are commonly used in conjunction with chromoendoscopy. The analysis of mucosal surface details is beginning to resemble histologic examination. More accurate recognition of small flat and depressed neoplastic lesions is possible. Endoscopic prediction of neoplastic and nonneoplastic tissue is possible by analysis of surface architecture of the mucosa, which influences the endoscopic management. For the diagnosis of flat adenomas, chromoendoscopy should be a part of the endoscopist's armamentarium. In inflammatory bowel disease, chromoendoscopy can be used for patients with long-standing UC to unmask flat intraepithelial neoplasia and is likely to become the new standard method for surveillance colonoscopy in the near future. The new detailed images seen with magnifying chromoendoscopy are the beginning of a new era in which advances in optical development, such as confocal endomicroscopy, allow a unique look at detailed cellular structures.

Kiesslich R, Hoffman A, Neurath MF. · Dept. of Medicine I, Johannes Gutenberg University, Mainz, Germany. ralf-kiesslich.de · Endoscopy. · Pubmed #16429347 No free full text.

Abstract: Accurate detection of premalignant lesions and early cancers in the colon is essential for curative endoscopic or surgical therapy, since the prognosis for the affected patients is closely related to the size and stage of the neoplastic lesion. Total colonoscopy is the accepted gold standard for screening and surveillance of colorectal cancer. This review summarizes recently published diagnostic developments and key findings in the areas of colonoscopy, colonic tumors, and inflammatory bowel diseases. Relevant findings have been reported for chromo-endoscopy in the diagnosis of colitis-associated neoplasia, as well as flat and depressed adenomas. Real-time Doppler capabilities have now been added to endoscopic optical coherence tomography; the results of large-scale testing of narrow-band imaging endoscopy in the colon are being awaited; and fluorescence imaging has recently been added to the facilities available in video endoscopy. Most importantly, endomicroscopy now for the first time allows single-cell subsurface imaging during ongoing colonoscopy procedures, opening the way to in-vivo molecular and functional imaging.

Kiesslich R, Neurath MF. · I. Med. Klinik und Poliklinik, Johannes Gutenberg Universität Mainz, Langenbeckstr. 1, Germany. · Best Pract Res Clin Gastroenterol. · Pubmed #16338651 No free full text.

Abstract: The prognosis for patients with malignancies of the lower gastrointestinal tract is strictly dependent on early detection of premalignant and malignant lesions. What should an ideal screening and surveillance colonoscopy be able to accomplish? The technique should allow detection of large but also discrete mucosal alterations. Ideally, endoscopic discrimination between neoplastic and non-neoplastic lesions would be possible during the ongoing procedure. At present, endoscopy can be performed with powerful new endoscopes. Comparable to the rapid development in chip technology, the optical features of the newly designed endoscopes offer resolutions, which allow new surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool video colonoscopy is much easier and more impressive today than with the previously used fibre-optic endoscopes. Recently, new endoscopic technologies such as narrow band imaging, endocytoscopy, or confocal laser endoscopy have allowed the discovery of a whole new world of image details which will surely improve the diagnostic yield in the field of early malignancies. This review summarises newly available technologies and clinical data about the diagnosis of early lower gastrointestinal cancers.

Kiesslich R, Goetz M, Vieth M, Galle PR, Neurath MF. · 1st Medical Clinic, Johannes Gutenberg University Mainz, Mainz, Germany. · Gastrointest Endosc Clin N Am. · Pubmed #16278135 No free full text.

Abstract: A miniaturized confocal microscope was developed that could be integrated in the distal tip of a conventional colonoscope. With this technique, denoted confocal endomicroscopy, subsurface analysis of the gut mucosa and in-vivo histology during ongoing endoscopy are possible in full resolution by point scanning laser analysis. The diagnostic spectrum of confocal endomicroscopy is expanding from screening and surveillance for colorectal cancer to Barrett's esophagus, Helicobacter pylori-associated gastritis, and gastric cancer. The new detailed images seen with confocal laser endomicroscopy allow a unique look on cellular structures at and below the surface of the gut. This review describes the optical and diagnostic possibilities of confocal laser endomicroscopy.

Kiesslich R, Neurath MF. · I Med Clinic, Johannes Gutenberg University of Mainz, Germany. · Clin Gastroenterol Hepatol. · Pubmed #16012999 No free full text.

Abstract: In vivo fluorescence endomicroscopy is a newly developed diagnostic tool enabling virtual in vivo histology of the mucosal layer during ongoing endoscopy. This review summarizes currently available data about the technique and clinical use of confocal endomicroscopy. Indications discussed include colorectal cancer evaluation, ulcerative colitis and surveillance, Barrett's esophagus, and detection of Helicobacter pylori infection in vivo.

Kiesslich R, Neurath MF. · Klinik und Poliklinik, Johannes Gutenberg Universität Mainz, Germany. · Eur J Gastroenterol Hepatol. · Pubmed #16003126 No free full text.

Abstract: It is essential to identify patients with premalignant or early malignant changes during colonoscopy. Thus, curative resection can be offered. At present, endoscopy can be performed with new powerful high-resolution or magnifying endoscopes. Comparably to the rapid development in chip technology, the optic features of the newly designed endoscopes offer resolutions which allow new mucosal surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool video endoscopy is much easier and more impressive than with conventional fibre optics. This review summarizes the value of magnifying endoscopy in the lower gastrointestinal tract and focuses on colorectal lesions.

Rutter M, Bernstein C, Matsumoto T, Kiesslich R, Neurath M. · University Hospital of North Tees, Hardwick, Stockton-on-Tees, Teesside, UK. · Endoscopy. · Pubmed #15578305 No free full text.

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Kiesslich R, Jung M, DiSario JA, Galle PR, Neurath MF. · I. Med. Klinik und Poliklinik, Johannes Gutenberg Universität Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. · J Clin Gastroenterol. · Pubmed #14679320 No free full text.

Abstract: The goal of every routine endoscopy in the gut is the early diagnosis of malignant and premalignant changes of the mucosa. Chromo- and magnifying endoscopes are exciting new tools and offer detailed analysis of the colonic mucosal surface and pit pattern architecture. This review summarizes recent advances in endoscopic characterization of colorectal lesions using magnification endoscopy and chromoendoscopy. Surface analysis of the colon using chromoendoscopy allows a prediction between non-neoplastic and neoplastic lesions with high specificity. The precise delineation of the borders and a more detailed macroscopic analysis of the lesions are further advantages. In particular, flat adenomas and early depressed cancers are now more frequently recognized in western countries suggesting that significant lesions were overlooked by conventional endoscopy in the past. Furthermore, chromoendoscopy can be used in a targeted fashion to screen for sporadic adenomas. Finally, in surveillance colonoscopy, patients with long-standing ulcerative colitis have a valuable benefit if targeted biopsies are performed to detect intraepithelial neoplasias after pan-chromoendoscopy with methylene blue. Although there is a long learning curve, chromoendoscopy should thus belong to every endoscopists armamentarium. However, detailed knowledge about the technique, dyes, and specific staining patterns are mandatory before the yield of screening or surveillance colonoscopy can be increased. The new detailed images seen with magnifying chromoendoscopy are unequivocally the beginning of a new era where new optical developments will allow a unique look on cellular structures.

Kiesslich R, Jung M. · I. Medizinische Klinik und Poliklinik, Johannes Gutenberg Universität Mainz. · Dtsch Med Wochenschr. · Pubmed #12970826 No free full text.

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Kiesslich R, Jung M, Galle PR, Neurath MF. · I. Med. Klinik und Poliklinik, Johannes Gutenberg Universität Mainz. · Dtsch Med Wochenschr. · Pubmed #12817350 No free full text.

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Kiesslich R, Fritsch J, Holtmann M, Koehler HH, Stolte M, Kanzler S, Nafe B, Jung M, Galle PR, Neurath MF. · I. Medical Clinic, Johannes Gutenberg University of Mainz, Mainz, Germany. · Gastroenterology. · Pubmed #12671882 No free full text.

Abstract: BACKGROUND & AIMS: Timely diagnosis of intraepithelial neoplasias (IN) and colitis-associated colon carcinomas (CRC) is crucially important for the treatment of ulcerative colitis (UC). We performed a randomized, controlled trial to test whether chromoendoscopy (CE) might facilitate early detection of IN and CRC in UC. METHODS: A total of 263 patients with long-standing UC (>or=8 years) were screened for potential inclusion in the study, 165 of whom were randomized at a 1:1 ratio to undergo conventional colonoscopy or colonoscopy with CE using 0.1% methylene blue. Five mucosal biopsy specimens were taken every 10 cm between the rectum and cecum. Circumscript lesions in the colon were evaluated according to a modified pit pattern classification. RESULTS: In the CE group, there was a significantly better correlation between the endoscopic assessment of degree (P = 0.0002) and extent (89% vs. 52%; P < 0.0001) of colonic inflammation and the histopathologic findings compared with the conventional colonoscopy group. More targeted biopsies were possible, and significantly more IN were detected in the CE group (32 vs. 10; P = 0.003). Using the modified pit pattern classification, both the sensitivity and specificity for differentiation between non-neoplastic and neoplastic lesions were 93%. CONCLUSIONS: Based on our prospective randomized trial, CE permits more accurate diagnosis of the extent and severity of the inflammatory activity in UC compared with conventional colonoscopy. In addition, CE with methylene blue is a novel tool for the early detection of IN and CRC in patients with UC. These findings have important implications for medical and surgical interventions.

Neurath MF, Kiesslich R. · I Medical Clinic and Institute of Molecular Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany. · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #19174765 No free full text.

Abstract: Chromoendoscopy was introduced in 2003 as a novel 'red flag' technique that aimed to increase the sensitivity of identifying flat, neoplastic lesions in patients with ulcerative colitis. The improved sensitivity of chromoendoscopy over standard white-light endoscopy has been confirmed in European and Asian centers. This commentary discusses the findings from a prospective, controlled study from the Mount Sinai Hospital in New York. The findings of this study provide unequivocal evidence that chromoendoscopy is superior to white-light endoscopy in the detection of neoplasias in patients with IBD. The authors of this study identified a greater number of lesions and a higher number of patients with dysplasia by use of this method and targeted biopsy sampling compared with standard endoscopy with random biopsy sampling. Chromoendoscopy in combination with targeted biopsies, therefore, has emerged as the new standard of cancer surveillance in patients with ulcerative colitis, and we can expect this technique to be incorporated into clinical guidelines shortly.

Kiesslich R, Galle PR, Neurath MF. · Johannes Gutenberg University of Mainz, Mainz, Germany. · Gastroenterology. · Pubmed #17854587 No free full text.

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Kiesslich R, Goetz M, Lammersdorf K, Schneider C, Burg J, Stolte M, Vieth M, Nafe B, Galle PR, Neurath MF. · I. Medical Clinic, Johannes Gutenberg University of Mainz, Germany. · Gastroenterology. · Pubmed #17383417 No free full text.

Abstract: BACKGROUND AND AIMS: Because of the large number of biopsy specimens, surveillance colonoscopy in ulcerative colitis (UC) is currently time consuming and significant flat lesions still may be missed. In this study we assessed the value of combined chromoscopy and endomicroscopy for the diagnosis of intraepithelial neoplasias in a randomized controlled trial. METHODS: A total of 161 patients with long-term UC in clinical remission were randomized at a 1:1 ratio to undergo conventional colonoscopy or chromoscopy with endomicroscopy. Eight patients were excluded because of insufficient bowel preparation. In the conventional colonoscopic group (n = 73), random biopsy examinations and targeted biopsy examinations were performed. In the endomicroscopy group (n = 80), circumscribed mucosal lesions were identified by chromoscopy and evaluated for targeted biopsy examination by endomicroscopy. The primary outcome analysis was based on the detection of neoplasias. RESULTS: By using chromoscopy with endomicroscopy, 4.75-fold more neoplasias could be detected (P = .005) than with conventional colonoscopy, although 50% fewer biopsy specimens (P = .008) were required. If only circumscribed lesions would have been biopsied in the first group, the total number of biopsy specimens could have been reduced by more than 90%. A total of 5580 confocal endomicroscopic images from 134 circumscribed lesions were compared with histologic results. The presence of neoplastic changes could be predicted by endomicroscopy with high accuracy (sensitivity, 94.7%; specificity, 98.3%; accuracy, 97.8%). CONCLUSIONS: Endomicroscopy based on in vivo histology can determine if UC lesions identified by chromoscopy should undergo biopsy examination, thereby increasing the diagnostic yield and reducing the need for biopsy examinations. Thus, chromoscopy-guided endomicroscopy may lead to significant improvements in the clinical management of UC.

Mudter J, Wirtz S, Weigmann B, Tiede I, Tubbe I, Kiesslich R, Galle PR, Lehr HA, Neurath MF. · First Medical Clinic, Johannes-Gutenberg-University, Mainz, Germany. · Dig Dis Sci. · Pubmed #16614993 No free full text.

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Mudter J, Weigmann B, Bartsch B, Kiesslich R, Strand D, Galle PR, Lehr HA, Schmidt J, Neurath MF. · Department of 1st Medical Clinic, Department of Pathology, Johannes-Gutenberg-University of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. · Am J Gastroenterol. · Pubmed #15654782 No free full text.

Abstract: OBJECTIVES: Cytokine signaling pathways involving transcription factors of the signal transducers and activators of transcription (STAT) family play a key role in the pathogenesis of inflammatory bowel diseases (IBD). STAT proteins are latent cytoplasmic transcription factors that induce transcription upon phosphorylation, dimerization, and nuclear translocation. However, their activation pattern in IBD is poorly understood. The aim of our study was to characterize STAT-expression in IBD. METHODS: Mononuclear cells were isolated from 36 colonic specimens of Crohn's disease, ulcerative colitis, or from control patients. Cells were stimulated overnight with antibodies against human CD2 and CD28 and mononuclear cells were analyzed by flow cytometry. Alternatively, CD4(+) T cells were immunomagnetically separated and then assessed by flow cytometry. Intracellular stainings of the following transcription factors were performed: STAT-1, STAT-2, STAT-3, STAT-4, and STAT-6. In addition, immunofluorescence staining on cryosections for phosphorylated STAT-1 and STAT-3 was performed. RESULTS: Average expression of the IFN-gamma inducible transcription factor STAT-1 was increased in Crohn's disease as compared to patients with ulcerative colitis and control patients. However, levels of phospho-STAT-1 were surprisingly not markedly upregulated in IBD as compared to controls. In contrast, STAT-3 and phospho-STAT-3 levels were significantly increased in IBD patients as compared to controls (p < 0.01). No differences could be detected in STAT-6 levels. Finally, average expression of STAT-2, which is involved in type I interferon signalling, was downregulated in IBD as compared to control patients. CONCLUSIONS: The analysis of STAT activation patterns could serve as a helpful tool to characterize intestinal inflammation. Furthermore, the IL-6/STAT-3 rather than the IFN-gamma/STAT-1 signaling pathway emerges as a key target for the development of future therapeutic concepts in IBD.

Kiesslich R, Neurath MF. · Medical Clinic, Johannes Gutenberg University of Mainz, Mainz, Germany. · Inflamm Bowel Dis. · Pubmed #15472537 No free full text.

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Kiesslich R, Neurath MF. · I Med Clinic, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. · Gut. · Pubmed #14724144 links to  free full text

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Hurlstone DP, Kiesslich R, Thomson M, Atkinson R, Cross SS. · Gastroenterology and Liver Unit at the Royal Hallamshire Hospital Sheffield/The Sheffield Hallam University Academy of Endomicroscopy, Sheffield, UK. · Gut. · Pubmed #18192453 No free full text.

Abstract: BACKGROUND: The diagnosis of intraepithelial neoplasia is pivotal for ongoing clinical management decisions in ulcerative colitis. Previous studies have compared the diagnostic yield of endomicroscopy with conventional "white light" endoscopy and hence the overall objective increase of endomicroscopy targeted biopsies as compared to chromoscopy guided alone is not apparent. AIMS: We performed a prospective randomised controlled study to compare the diagnostic yield of intraepithelial neoplasia and cancer in patients undergoing ulcerative colitis screening using chromoscopy assisted endomicroscopy (group A) versus pan-colonic chromoscopy assisted colonoscopy (group B). METHODS: Patients were randomised in a 1:1 ratio to undergo screening colonoscopy using either chromoscopic endomicroscopy or chromoscopy alone with targeted biopsies. Circumscribed lesions were characterised using endomicroscopy and chromoscopy with pit pattern analysis. Targeted biopsies in addition to conventional 10 cm quadrantic biopsies were taken. Primary outcome addressed the number of intraepithelial neoplasias detected in each group. RESULTS: Endomicroscopy targeted biopsies significantly increased the yield of intraepithelial neoplasia as compared to pan-chromoscopy and biopsy alone (p<0.001) and also increased the yield of high-grade dysplastic lesions (p<0.001). Endomicroscopy targeted biopsies increased the diagnostic yield of intraepithelial neoplasia as compared to chromoscopy guided biopsies alone by 2.5-fold. CONCLUSIONS: This is the first randomised controlled study to show the true clinical benefit of endomicroscopy for the in vivo detection and characterisation of intraepithelial neoplasia in chronic ulcerative colitis surveillance colonoscopy. Endomicroscopy with targeted biopsy may potentially be the "gold standard" for the detection of intraepithelial neoplasia in ulcerative colitis.