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Ralf Kiesslich

Publications and source records attributed to Ralf Kiesslich.

18 recordsLinked to original sources
PubMed2006

In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy.

BACKGROUND & AIMS: Confocal laser endomicroscopy allows subsurface analysis of the intestinal mucosa and in vivo histology during ongoing endoscopy. Here, we have applied this technique to the in vivo diagnosis of Barrett's epithelium and associated neoplasia. METHODS: Fluorescein-aided endomicroscopy was performed by applying the endomicroscope over the whole columnar-lined lower esophagus. Images obtained within 1 cm of the columnar-lined lower esophagus were stored digitally and a targeted biopsy examination or endoscopic mucosal resection of the examined areas was performed. In vivo histology was compared with the histologic specimens. All digitally stored images were re-assessed by a blinded investigator by the confocal Barrett classification system to predict histology. Intraobserver and interobserver variations of the involved endoscopists were evaluated by using kappa statistics. RESULTS: Endomicroscopy allowed distinguishing between different types of epithelial cells and detected cellular and vascular changes in Barrett's epithelium at high resolution during ongoing endoscopy in 63 patients. Barrett's esophagus and associated neoplasia could be predicted with a sensitivity of 98.1% and 92.9% and a specificity of 94.1% and 98.4%, respectively (accuracy, 96.8% and 97.4%). The mean kappa value for interobserver agreement for the prediction of histopathological diagnosis was .843, whereas the intraobserver agreement showed a mean kappa value of .892. CONCLUSIONS: Fluorescence-aided endomicroscopy of Barrett's esophagus allows in vivo histology of the mucosal layer during ongoing endoscopy. Gastric and Barrett's epithelium and Barrett's-associated neoplastic changes can be diagnosed with high accuracy. Thus, endomicroscopy may be helpful in the management of patients with Barrett's esophagus.

Barrett Esophagus↗
PubMed2006

Chromoendoscopy and other novel imaging techniques.

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.

Chromogenic Compounds↗
PubMed2006

Drug insight: novel small molecules and drugs for immunosuppression.

Gastrointestinal diseases can result from the inadequate or excessive response of the immune system to self or innocuous antigens. Moreover, the physiologic activation of the immune system against non-self antigens is a major clinical problem in liver organ transplantation. At present, many drugs are available that suppress the activation of the immune system, although most of the currently used immunosuppressive drugs lack specificity in terms of their molecular targets and, therefore, have the potential to generate numerous side effects. The advances that have been made in understanding the molecular events that underlie the activation of the immune system have led to the development of a new generation of 'small molecules' that are endowed with immunosuppressive properties and can serve as immunomodulatory agents. Among these new small molecules, inhibitors of Janus kinase 3, p21-Rac1 and p38 mitogen-activated protein kinase represent the most innovative approach to immunosuppression, and could be a promising alternative to current immunosuppressive therapies. Here, we report on the progress that has been made in the development of small molecules in the field of gastroenterology.

Animals↗
PubMed2006

Confocal laser endoscopy: new approach to the early diagnosis of tumors of the esophagus and stomach.

The prognosis of malignancies of the upper gastrointestinal tract is poor if early diagnosis is missed. Therefore, a rapid in vivo diagnosis of early cancer and premalignant lesions is highly important for successful therapy. Confocal laser endomicroscopy allows in vivo cellular and subcellular imaging at high resolutions during ongoing endoscopy. The first studies and clinical observations suggest a major role of this novel technique in the in vivo diagnosis of cancer of the esophagus and stomach and of precursor conditions, such as Barrett's esophagus, intestinal metaplasia of the stomach and Helicobacter pylori infection. Based on recent experiences from animal models, future studies will approach in vivo molecular imaging of human cancer.

Endoscopy, Gastrointestinal↗
PubMed2005

A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract.

BACKGROUND: This report describes the development and the clinical evaluation of a novel confocal endomicroscope for obtaining fluorescence images of cellular morphology of the mucosae of the upper- and the lower-GI tract in vivo. The work assessed the feasibility of performing in vivo microscopy at endoscopic examination and evaluated fluorescence imaging protocols. METHODS: Images were collected in real time by using two prototype endoscope configurations, featuring slightly different miniaturized fiber-optic confocal microscopes, fitted integrally into the tips of conventional endoscopes. Confocal scanning was performed at 488 nm illumination for excitation of exogenously applied fluorophores (topical acriflavine and intravenous fluorescein). The images were compared with conventional histology of biopsy specimens and the findings of white-light endoscopy. RESULTS: Confocal endomicroscopy enabled imaging of cellular and subcellular structures (i.e., nuclei) of the GI tract. The crypts of the colonic mucosa, the villi of the terminal ileum and duodenum, the gastric pits of the stomach, and the squamous epithelium of the distal esophagus could be clearly visualized. Acriflavine strongly contrasted the cell nuclei of the surface epithelium, including the absorptive epithelial cells and the mucous secreting goblet cells. Fluorescein stained the extracellular matrix of the surface epithelium and also the subepithelial layers of the lamina propria. Images at increasing depth beneath the epithelium showed the mucosal capillary network. The findings correlated with the histology of biopsy specimens. CONCLUSIONS: The development of a fluorescence confocal endomicroscope makes it practical to examine the upper- and the lower-GI mucosa in cellular detail during otherwise routine endoscopic examination. The results represent a major technical advance in the development of this new optical imaging modality for the in vivo examination of GI tissue.

Acriflavine↗
PubMed2005

Confocal laser endomicroscopy.

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.

Acriflavine↗
PubMed2005

Endoluminal therapy of GERD with a new endoscopic suturing device.

BACKGROUND: Endoscopic, endoluminal therapy might be an alternative treatment option in light of the costs of proton pump inhibitor therapy and possible complications after laparoscopic surgery. The aim of the current study was to assess the efficacy and the safety of a new endoluminal suture device (ESD) in pig models and humans. Secondly, 3 and 6 months' follow-ups were performed, and possible complications and their management were evaluated. METHODS: In the preclinical phase of the study, suturing procedures were practiced and evaluated in 8 pig models (Erlanger Endo Trainer). In the clinical phase, 20 patients with mild esophagitis, small or no hiatal hernia, and signs of abnormal acid exposure (pH measurements) were enrolled. Therapeutic endoscopy (propofol sedation) was performed with the flexible suture and the Ti-Knot devices, which were introduced over an external accessory channel, fixed on the endoscope. One to 3 sutures were applied per patient at the gastroesophageal junction. A 3 months' follow-up included upper endoscopy, manometry, 24-hour pH study, and clinical questionnaires. RESULTS: Visibility with the new device was good, and, in all cases, sutures could be applied with only minor complications. In the animal model, the stitches reached the muscularis propria. However, the 3-month follow-up showed that only 12% of all plications persisted over this short period in humans. In addition, the clinical response was poor (no significant changes after the procedure: pH study, proton pump inhibitor intake, lower-esophageal sphincter pressure on manometry). In two patients, acute bleeding occurred, which was successfully controlled with endoscopic therapy. However, these patients were observed overnight in the hospital without further complications. The study was interrupted after 3 months because of the results of the interim analysis. CONCLUSIONS: The new endoscopic suturing device allows a feasible and safe technique for application of endoscopic sutures. The procedure could be performed on an outpatient basis by using sedation with propofol. However, the clinical outcome was very limited because of the high number of lost or failed plications. Thus, the ESD currently cannot be recommended in the treatment of patients with GERD.

Adolescent↗
PubMed2005

Endoscopic confocal imaging.

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.

Diagnosis, Differential↗
PubMed2005

6-thioguanosine diphosphate and triphosphate levels in red blood cells and response to azathioprine therapy in Crohn's disease.

BACKGROUND & AIMS: Azathioprine is the gold standard for immunosuppressive therapy in Crohn's disease (CD) and its molecular mechanism of action is caused by the metabolite 6-thioguanosine triphosphate (TGTP). In this study we assessed the impact of TGTP levels for monitoring of azathioprine therapy. METHODS: A novel, highly sensitive assay was established to measure levels of TGTP and its precursors 6-thioguanosine monophosphates and 6-thioguanosine diphosphates (TGDP) in red blood cells from 50 CD patients. The results were correlated with clinical outcome. RESULTS: TGTP levels could be quantified in 47 patients and a subgroup of these patients showed significantly high levels of TGDP. 6-thioguanine nucleotide (6-TGN) levels showed a significant correlation with TGDP plus TGTP concentrations, suggesting that active TGTP and its inactive precursor TGDP are the main metabolites within 6-TGN. Patients with 6-TGN levels higher than 100 pmol/8x10(8) red blood cells showed better response rates, on average, than patients with lower 6-TGN levels. The subgroup of patients with higher 6-TGN and increased TGDP levels showed a worse outcome with lower response rates, more flares, and higher infliximab demand than patients with high 6-TGN, low TGDP, and predominantly detectable TGTP levels. CONCLUSIONS: This study shows that quantification of TGTP levels can be used to monitor azathioprine therapy in inflammatory bowel disease patients. Furthermore, the data suggest that TGDP levels of more than 15% of total 6-TGN levels may be a useful surrogate parameter to predict poor response in a subgroup of azathioprine-treated patients.

Adult↗
PubMed2005

Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy.

BACKGROUND & AIMS: Confocal laser endomicroscopy enables subsurface microscopic imaging of living tissue during ongoing endoscopy. This case report describes the in vivo detection of Helicobacter pylori by endomicroscopy. METHODS: Endomicroscopy (Pentax, Tokyo, EC-3870CIFK) was performed by using two different contrast stains: Topical Acriflavine in addition to intravenously applied fluorescein netted the surface and allowed identification of focal accumulation of Helicobacter pylori at the surface and in deeper layer of the gastric epithelium. Biopsies were performed at the antrum and corpus for urease testing and histology. In addition, biopsies were cultured for Helicobacter pylori. Cultured bacteria were re-assessed ex vivo using confocal microscopy with and without acriflavine staining. RESULTS: Helicobacter pylori infection could be detected in a 70-year-old male by endomicroscopy. Accumulated, as well as single bacteria, could be observed and the distinct shape and flagella of Helicobacter pylori could be identified. Helicobacter pylori infection was proved by histology. Furthermore, ex vivo examination of cultures proved the presence of Helicobacter pylori and the active uptake of acriflavine into the bacteria. CONCLUSIONS: Endomicroscopy is a new diagnostic approach, which enables the immediate diagnosis of Helicobacter pylori in vivo during standard video endoscopy.

Acriflavine↗
PubMed2005

Chromo- and magnifying endoscopy for colorectal lesions.

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.

Adenoma↗
PubMed2005

Activation pattern of signal transducers and activators of transcription (STAT) factors in inflammatory bowel diseases.

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.

CD4-Positive T-Lymphocytes↗
PubMed2004

TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling.

Alterations of TGF-beta signaling have been described in colorectal cancer, although the molecular consequences are largely unknown. By using transgenic mice overexpressing TGF-beta or a dominant-negative TGF-betaRII, we demonstrate that TGF-beta signaling in tumor infiltrating T lymphocytes controls the growth of dysplastic epithelial cells in experimental colorectal cancer, as determined by histology and a novel system for high-resolution chromoendoscopy. At the molecular level, TGF-beta signaling in T cells regulated STAT-3 activation in tumor cells via IL-6. IL-6 signaling required tumor cell-derived soluble IL-6R rather than membrane bound IL-6R and suppression of such TGF-beta-dependent IL-6 trans-signaling prevented tumor progression in vivo. Taken together, our data provide novel insights into TGF-beta signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on inhibition of TGF-beta-dependent IL-6 trans-signaling.

Animals↗
PubMed2004

Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo.

BACKGROUND & AIMS: A confocal laser endoscopy system has recently been developed that may allow subsurface imaging of living cells in colonic tissue in vivo. The aim of the present study was to assess its potential for prediction of histology during screening colonoscopy for colorectal cancer. METHODS: Twenty-seven patients underwent colonoscopy with the confocal endoscope using acriflavine hydrochloride or fluorescein sodium with blue laser illumination. Furthermore, 42 patients underwent colonoscopy with this system using fluorescein sodium. Standardized locations and circumscript lesions were examined by confocal imaging before taking biopsy specimens. Confocal images were graded according to cellular and vascular changes and correlated with conventional histology in a prospective and blinded fashion. RESULTS: Acriflavine hydrochloride and fluorescein sodium both yielded high-quality images. Whereas acriflavine hydrochloride strongly labeled the superficial epithelial cells, fluorescein sodium offered deeper imaging into the lamina propria. Fluorescein sodium was thus used for the prospective component of the study in which 13,020 confocal images from 390 different locations were compared with histologic data from 1038 biopsy specimens. Subsurface analysis during confocal laser endoscopy allowed detailed analysis of cellular structures. The presence of neoplastic changes could be predicted with high accuracy (sensitivity, 97.4%; specificity, 99.4%; accuracy, 99.2%). CONCLUSIONS: Confocal laser endoscopy is a novel diagnostic tool to analyze living cells during colonoscopy, thereby enabling virtual histology of neoplastic changes with high accuracy. These newly discovered diagnostic possibilities may be of crucial importance in clinical practice and lead to an optimized rapid diagnosis of neoplastic changes during ongoing colonoscopy.

Acriflavine↗
PubMed2004

Chromoendoscopy and magnifying endoscopy in patients with gastroesophageal reflux disease. Useful or negligible?

Gastroesophageal reflux disease (GERD) is common in the Western world. Upper endoscopy is needed to characterize the disease. Barrett's esophagus as a complication of GERD is an established precancerous condition which can lead to adenocarcinoma in the distal esophagus. This review summarizes recent advances in the endoscopic characterization of Barrett's esophagus using magnification endoscopy and chromoendoscopy. Methylene blue, indigo carmine and acetic acid are commonly used dyes to facilitate diagnosis of Barrett's esophagus. Methylene blue is absorbed in the specialized columnar epithelium, which is pathognomonic for Barrett's esophagus. Indigo carmine and acetic acid are used as contrast stains to highlight the surface architecture. Currently, different dyes are used in conjunction with magnifying endoscopes to characterize specific surface patterns of Barrett's epithelium. However, the current proposed classifications are too complex relative to their clinical value. Nevertheless, simplification of these systems will occur over time with increased use of magnifying chromoendoscopy. The value of magnifying chromoendoscopy for clinical practice is not determined yet and currently under investigation. However, these techniques have significant potential to improve diagnostic accuracy in patients with Barrett's esophagus.

Acetic Acid↗
PubMed2003

Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis.

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.

Adult↗
PubMed2003

Mini-laparoscopically guided percutaneous gastrostomy and jejunostomy.

BACKGROUND: Percutaneous endoscopic tube placement can be problematic under certain circumstances: absence of transillumination of the abdominal wall, percutaneous jejunostomy in patients with a PEG tube and recurrent aspiration, enteral feeding access after gastrectomy, and obstruction of the upper GI tract. As an alternative in these problematic situations, a technique was developed for placing feeding tubes under visual control by using mini-laparoscopy. METHODS: Placement of a feeding tube with mini-laparoscopy with the patient under conscious sedation was considered for 17 patients in whom standard PEG placement was impossible. Techniques used were the following: combined mini-laparoscopy/endoscopy for placement of a percutaneous gastrostomy or jejunostomy, and mini-laparoscopic-guided direct tube placement in cases of obstruction of the upper GI tract. OBSERVATIONS: In 13 patients, mini-laparoscopic-assisted tube placement was successful. In 4 patients, adhesions or peritoneal carcinomatosis prevented laparoscopic visualization of the stomach or small bowel. The combined mini-laparoscopic/endoscopic approach allowed a successful insertion of gastric tubes in 6 patients and jejunal tubes in 4 patients. Direct insertion of a percutaneous endoscopic jejunostomy tube without enteroscopy was feasible in all 3 patients with obstruction of the upper GI tract. No complication occurred. CONCLUSIONS: Mini-laparoscopy-assisted tube placement is a simple and safe alternative when endoscopic percutaneous tube placement is problematic or not feasible.

Adult↗