High-definition endoscopy with iScan and Lugol's solution for the detection of inflammation in patients with nonerosive reflux disease: histologic evaluation in comparison with a control group.

Nonerosive reflux disease (NERD) is commonly diagnosed in patients with symptoms of reflux. The aim of the present study was to determine whether high-definition endoscopy (HD) plus equipped with the iScan function or chromoendoscopy with Lugol's solution might permit the differentiation of NERD patients from those without reflux symptoms, proven by targeted biopsies of endoscopic lesions. A total of 100 patients without regular intake of proton pump inhibitors and with a normal conventional upper endoscopy were prospectively divided into NERD patients and controls. A second upper endoscopy was performed using HD+ with additional iScan function and then Lugol's solution was applied. Biopsy specimens were taken from the gastroesophageal junction in all patients. A total of 65 patients with reflux symptoms and 27 controls were included. HD(+) endoscopy with iScan revealed subtle mucosal breaks in 52 patients; the subsequent biopsies confirmed esophagitis in all cases. After Lugol's solution, 58 patients showed mucosal breaks. Sensitivity for the iScan procedure was 82.5%, whereas that for Lugol's solution was 92.06%. Excellent positive predictive values of 100% and 98.3%, respectively, were noted. The present study suggests that the majority of patients with NERD and typical symptoms of reflux disease can be identified by iScan or Lugol's chromoendoscopy as minimal erosive reflux disease (ERD) patients.

[Catch me if you can: endoscopic remove of a needle from the jejunum]. / Catch me if you can: Endoskopische Bergung einer Sicherheitsnadel aus dem tiefen Dünndarm.

INTRODUCTION: The ingestion of foreign bodies is a frequently observed problem in daily clinical practice. In order to avoid complications such as perforation, endoscopic removal of potentially penetrating foreign bodies should be attempted quickly. The use of various endoscopic techniques has been reported for this purpose. However, extraction of foreign bodies from the mid gastrointestinal tract has rarely been reported. CASE REPORT: We present the case of a patient who had swallowed a safety needle which could safely be removed from the jejunum by means of double-balloon enteroscopy (DBE). The combination of a thin p-type enteroscope with a thick t-type overtube was used in order to improve the manoeuvrability of the endoscope. The needle was pulled into the overtube which served as a protective shield during the retrieval of the endoscope. CONCLUSION: Our case report describes the potential of removing foreign bodies from the deep small bowel by pulling them into the overtube of a double-balloon enteroscope. If the suspicion of foreign body impaction in the small bowel is made, it may be advisable to primarily choose a balloon enteroscopy system. Through this, quick and deep insertion can be combined with a safe removal of the foreign body.

[Incidental findings in gastroscopy and colonoscopy]. / Zufallsbefunde in Gastroskopie und Koloskopie.

For many specific and nonspecific gastrointestinal symptoms, endoscopic diagnostic procedures play an important role. Gastroscopy and colonoscopy are easily available diagnostic and interventional procedures with low risk. The technical development of gastrointestinal endoscopy has led to an improvement in diagnostics and therapy. In addition to frequent and expected findings, incidental findings may occur. The incidental findings can distinguish rare diseases of unexpected diagnoses. Rare diagnoses usually require an individualized therapy. Unexpected diagnoses can take place during (not properly detected) or after an endoscopy (overlooked or newly appeared) occur. This overview deals with the question of how to minimize unexpected diagnoses and how to diagnose and treat incidental findings.

[Upper gastrointestinal bleeding and haemorrhagic shock at the end of the holidays: pre-hospital and in-hospital management of a gastrointestinal emergency]. / Obere gastrointestinale Blutung mit hämorrhagischem Schock am Ende einer Urlaubsreise: Präklinische und innerklinische Versorgung eines gastrointestinalen Notfalls.

Upon returning from holidays, a 55-year-old patient presenting with melena and haemorrhagic shock was admitted to a University hospital after receiving first emergency medical care in a German InterCity train. In an interdisciplinary effort, haemodynamics were stabilised and the airway and respiratory function were secured. Under emergency care conditions the patient then underwent an emergency upper GI endoscopy where a spurting arterial upper gastrointestinal bleeding (Forrest 1a) was found. While the bleeding could not be controlled with endoscopic techniques, definitive haemostasis was achieved with a surgical laparotomy. While not commonly established for patients with severe GI bleeding, by spontaneous implementation of an interdisciplinary trauma room approach following established trauma algorithms the team was able to achieve stabilisation of vital functions and final control of bleeding in this highly unstable patient. Although the majority of upper gastrointestinal bleedings spontaneously cease, emergency care algorithms should be developed and implemented for patients with severe gastrointestinal bleedings in shock. Following the case vignette, we discuss a potential approach and develop an exemplary protocol for shock room management in this patient subgroup.

In vivo molecular imaging with cetuximab, an anti-EGFR antibody, for prediction of response in xenograft models of human colorectal cancer.

BACKGROUND AND STUDY AIMS: Molecular imaging has mainly been studied for detection of lesions using diagnostic probes. The aim of the current trial was to evaluate in vivo confocal laser endomicroscopy (CLE) with cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), for detection and moreover early prediction of response to molecular chemotherapy in models of human colorectal cancer (CRC). METHODS: Xenografts with cetuximab-sensitive (HT29) and cetuximab-resistant (SW620) human CRC cell lines were induced in 44 mice. CLE was performed 48 h after injection of a fluorescently labelled cetuximab test dose, and compared with isotype antibody or untreated controls on d0, and d30 (HT29) or d15 (SW620). Initial fluorescence intensity was examined in relation to clinical readouts (tumor growth, thriving, mortality) during cetuximab treatment vs. controls. Results were validated in vivo with wide-field molecular imaging in three HT29 mice and ex vivo using fluorescence-activated cell sorting (FACS) and immunohistochemistry. RESULTS: All HT29 xenografts showed specific fluorescence in vivo after cetuximab injection on d0 and d30. Fluorescence at d0 was significantly stronger in cetuximab-treated HT29 tumors than in HT29 controls (P = 0.0017) or cetuximab-treated SW620 tumors (P = 0.0027), and accorded with significantly slower tumor progression (P = 0.0009), better overall survival (P = 0.02), and better physical condition (P < 0.0001). Cetuximab sensitivity could be predicted from fluorescence intensity at d0 with high positive predictive value. CONCLUSIONS: Molecular CLE was for the first time linked to early prediction of response to targeted therapy in models of human CRC. Therapeutic antibodies can be used as molecular beacons in CLE and wide-field techniques. These results may indicate a promising principle for early patient stratification.

In vivo molecular imaging of gastric cancer by targeting MG7 antigen with confocal laser endomicroscopy.

BACKGROUND AND STUDY AIMS: In vivo molecular imaging represents a powerful tool for the immediate diagnosis of gastric cancer. In this study, the monoclonal antibody MG7, which is a specific molecular marker against gastric cancer, was labeled with fluorescent agents to enable in vivo real-time imaging by confocal laser endomicroscopy (CLE). PATIENTS AND METHODS: In vivo molecular imaging was performed in tumor-bearing mice from two kinds of human gastric cancer cell lines. Xenograft tumors were visualized in vivo first with a whole-body fluorescent imaging device and then by CLE using fluorescently labeled MG7 antibody. Gastric cancerous tissue and noncancerous mucosa from human biopsies or surgical specimens were also examined ex vivo by CLE. RESULTS: Intravital imaging of xenograft tumors revealed a specific cellular signal, whereas no specific signal was observed in control tissue or in mice injected with irrelevant antibodies. An ex vivo experiment on human specimens using a rigid confocal probe showed positive fluorescent staining in 22/23 samples diagnosed as gastric cancer and weak signals in 5/23 noncancerous tissue samples. CLE evaluation correlated well with immunohistochemical findings. CONCLUSIONS: Screening tumors in vivo by CLE may help to detect MG7-Ag-positive tissues, decrease the sampling error by screening the large tumor surface not routinely screened by biopsy or conventional immunohistochemistry, and facilitate early detection of gastric carcinoma.

[Diagnosis and treatment of esophageal cancer]. / Diagnostik und Therapie des Ösophaguskarzinoms.

The prognosis for patients with advanced esophageal cancer is poor. Proper risk assessment and knowledge of tumor biology may facilitate early diagnosis of adenocarcinomas and squamous cell cancer of the esophagus. New endoscopic techniques are available (e.g., (virtual) chromoendoscopy, autofluorescence, and endomicroscopy) for the early detection of cancer. Endoscopic therapy with complete resection of mucosal cancers offers long-term survival.En bloc resection combined with the removal of locoregional lymph nodes is the surgical option of choice for locally advanced cancer. In this respect, minimally invasive surgery offers the patient numerous advantages. Multimodal therapy results in better outcome for defined cancer stages and includes surgery, chemotherapy and chemoradiation. Multimodal treatment should always be individualized and requires cooperation of all subspecialties (tumor board conference). New chemotherapeutic strategies may offer improved survival but may also include new side effects. Patients with inoperable esophageal cancer also benefit from multimodal treatment.

MedJet--a new CO2-based disposable cleaning device allows safe and effective bowel cleansing during colonoscopy: a pilot study.

BACKGROUND AND STUDY AIMS: Complete bowel cleansing is mandatory for effective colon cancer screening and surveillance. The aim of the current pilot study, which was conducted in humans, was to test the safety and efficiency of a newly developed disposable cleaning device, the MedJet, for intraprocedural bowel cleansing. PATIENTS AND METHODS: Patients with screening or surveillance colonoscopy after previous polypectomy were included. The colonoscope was first inserted to the cecum and the overall cleansing was assessed according to the Ottawa scale. The MedJet device was used if colon cleansing had been incomplete. The MedJet catheter was passed over the working channel of the colonoscope and the colon was cleaned during withdrawal. The MedJet device delivered controlled jets comprising compressed CO2 and minimal amounts of sterile water, which allowed disintegration and removal of residual stool. The efficiency of cleaning was assessed according to the Boston scale. RESULTS: A total of 32 patients (16 female; mean age 61 years) were treated with the device. No device-related adverse or serious adverse events were noted. MedJet application during withdrawal provided effective and significant improvement in bowel cleansing (P = 0.005). Furthermore, 18 adenomas and 1 colon cancer, which were hidden behind stool remnants, could be identified in 11 patients following use of the MedJet device. However, the withdrawal times were prolonged (11.4±6.0 minutes) due to the additional cleaning procedure. All patients tolerated the procedure well. CONCLUSIONS: The new MedJet device enabled highly effective and safe bowel cleansing during colonoscopy. The catheter-based system was easy to use and CO2 was applied for cleansing. The procedure was well tolerated by patients.

Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease.

OBJECTIVES: Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD. METHODS: Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease. RESULTS: Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p<0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively. CONCLUSIONS: Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.

Review article: in vivo imaging by endocytoscopy.

BACKGROUND: Endocytoscopy (EC) enables in vivo microscopic imaging at 1400-fold magnification, thereby allowing the analysis of mucosal structures at the cellular level. In contrast to fluorescence imaging with confocal laser endomicroscopy which allows analysis of mucosal structures up to 250 µm in depth, EC is based on the principle of contact light microscopy and only allows visualisation of the very superficial mucosal layer. AIM: To systematically review the feasibility and diagnostic yield of EC for in vivo diagnosis of diseases. METHODS: A systematic search of the literature on diagnostic interventions in the gastrointestinal tract using EC was performed by searches in MEDLINE, Current Contents, PubMed, cross-references and references from relevant articles using the search terms 'endocytoscopy', 'endocytoscope', 'magnification endoscopy', 'endocytoscopic imaging', 'virtual histology' and 'optical biopsy'. Only full manuscripts and case reports published in English were included. RESULTS: Overall twenty-nine relevant reports were identified. EC was feasible to detect oesophageal squamous cell cancer with sensitivity, specificity and accuracy of 95%, 84% and 82%, respectively. Moreover, EC reached excellent sensitivity and specificity for in vivo diagnosis of colon polyps (91% and 100%, respectively). Other diagnostic applications of EC included diagnosis of Barrett's oesophagus, Helicobacter pylori, coeliac disease and small cell lung cancer. No serious complications of EC have yet been reported. CONCLUSIONS: Endocytoscopy is a safe and effective new endoscopic imaging technique to obtain in vivo histology and guided biopsies with high diagnostic accuracy. Therefore, endocytoscopy has the potential to facilitate both diagnosis and patient management.

High definition colonoscopy combined with i-Scan is superior in the detection of colorectal neoplasias compared with standard video colonoscopy: a prospective randomized controlled trial.

INTRODUCTION: Colonoscopy is the accepted gold standard for the detection of colorectal cancer. The aim of the current study was to prospectively compare high definition plus (HD+) colonoscopy with I-Scan functionality (electronic staining) vs. standard video colonoscopy. The primary endpoint was the detection of patients having colon cancer or at least one adenoma. METHODS: A total of 220 patients due to undergo screening colonoscopy, postpolypectomy surveillance or with a positive occult blood test were randomized in a 1 : 1 ratio to undergo HD+ colonoscopy in conjunction with I-Scan surface enhancement (90i series, Pentax, Tokyo, Japan) or standard video colonoscopy (EC-3870FZK, Pentax). Detected colorectal lesions were judged according to type, location, and size. Lesions were characterized in the HD+ group by using further I-Scan functionality (p- and v-modes) to analyze pattern and vessel architecture. Histology was predicted and biopsies or resections were performed on all identified lesions. RESULTS: HD+ colonoscopy with I-Scan functionality detected significantly more patients with colorectal neoplasia (38 %) compared with standard resolution endoscopy (13 %) (200 patients finally analyzed; 100 per arm). Significantly more neoplastic (adenomatous and cancerous) lesions and more flat adenomas could be detected using high definition endoscopy with surface enhancement. Final histology could be predicted with high accuracy (98.6 %) within the HD+ group. CONCLUSIONS: HD+ colonoscopy with I-Scan is superior to standard video colonoscopy in detecting patients with colorectal neoplasia based on this prospective, randomized, controlled trial.

[Molecular imaging of the small intestine]. / Molekulare Bildgebung: Was kann sie für den Dünndarm bringen?

Molecular imaging uses the molecular signature of cells for targeted minimally-invasive detection and characterization of gastrointestinal pathologies. Exogenous fluorescent agents serve as molecular beacons for visualization of specific surface markers or metabolic activity in the target tissue. Molecular imaging with radioactively labeled substances is well established in nuclear medicine for wide-field detection of lesions in the small intestine. In gastrointestinal endoscopy, both macroscopic detection by endogenous or exogenous fluorescence and microscopic visualization by endomicroscopy have been investigated in clinical trials, however have not yet been evaluated in larger patient cohorts. Still, molecular imaging has the potential to greatly enhance our understanding of gastrointestinal pathology and to impact on future clinical algorithms and science in gastroenterology.

In vivo molecular imaging of somatostatin receptors in pancreatic islet cells and neuroendocrine tumors by miniaturized confocal laser-scanning fluorescence microscopy.

The aim of the study was to evaluate real time in vivo molecular imaging of somatostatin receptors (sstrs) using a handheld miniaturized confocal laser scan microscope (CLM) in conjunction with fluorescein-labeled octreotate (OcF) in healthy mice and murine models of neuroendocrine tumors. For CLM a small rigid probe (diameter 7 mm) with an integrated single line laser (488 nm) was used (optical slice thickness 7 mum; lateral resolution 0.7 mum). OcF was synthesized via Fmoc solid-phase peptide synthesis and purified by HPLC showing high-affinity binding to the sstr2 (IC(50) 6.2 nmol). For in vitro evaluation, rat and human pancreatic cancer cells were used and characterized with respect to its sstr subtype expression and functional properties. For in vivo confocal imaging, healthy mouse pancreatic islet and renal tubular cells as well as immunoincompetent nude mice harboring sstr-expressing tumors were evaluated. Incubation of sstr-positive cells with OcF showed a specific time- and dose-dependent staining of sstr-positive cells. CLM showed rapid internalization and homogenous cytoplasmatic distribution. After systemic application to mice (n = 8), specific time-dependent internalization and cytoplasmatic distribution into pancreatic islet cells and tubular cells of the renal cortex was recorded. After injection in tumor-harboring nude mice (n = 8), sstr-positive cells selectively displayed a cell surface and cytoplasmatic staining. CLM-targeted biopsies detected sstr-positive tumor cells with a sensitivity of 87.5% and a specificity of 100% as correlated with ex vivo immunohistochemistry. CLM with OcF permits real-time molecular, functional, and morphological imaging of sstr-expressing cell structures, allowing the specific visualization of pancreatic islet cells and neuroendocrine tumors in vivo.

The safety of intravenous fluorescein for confocal laser endomicroscopy in the gastrointestinal tract.

BACKGROUND: Confocal laser endomicroscopy (CLE) is rapidly emerging as a valuable tool for gastrointestinal endoscopic imaging. Fluorescent contrast agents are used to optimize imaging with CLE, and intravenous fluorescein is the most widely used contrast agent. Fluorescein is FDA-cleared for diagnostic angiography of the retina. For these indications, the safety profile of fluorescein has been well-documented; however, to date, fluorescein is not cleared for use with CLE. AIMS: To estimate the rate of serious and total adverse events attributable to intravenous fluorescein when used for gastrointestinal CLE. METHODS: We performed a cross sectional survey of 16 International Academic Medical Centres with active research protocols in CLE that involved intravenous fluorescein. Centres using i.v. fluorescein for CLE who were actively monitored for adverse events were included. RESULTS: Sixteen centres performed 2272 gastrointestinal CLE procedures. The most common dose of contrast agent was 2.5-5 mL of 10% sodium fluorescein. No serious adverse events were reported. Mild adverse events occurred in 1.4% of individuals, including nausea/vomiting, transient hypotension without shock, injection site erythema, diffuse rash and mild epigastric pain. The limitation is that only immediate post procedure events were actively monitored. CONCLUSIONS: Use of intravenous fluorescein for gastrointestinal CLE appears to be safe with few acute complications.

Recognition and characterization of small colonic neoplasia with high-definition colonoscopy using i-Scan is as precise as chromoendoscopy.

BACKGROUND: The EPKi system (Pentax, Japan) enables resolution above HDTV. Aim of the study was to test the efficacy of HD+ alone and with the new post-processing digital filter i-Scan or chromoendoscopy (Methylene blue 0.1%) in screening for colorectal cancer. We focused on lesions less than 5 mm as a surrogate marker for the optical possibilities of the EPKi system. METHODS: The last 30 cm of the colon in a screening population were inspected with HD+ alone, in combination with i-Scan (2:1 randomisation) and subsequently with chromoendoscopy. All lesions were characterized and targeted biopsies were performed. RESULTS: i-Scan augmented in 69 patients the identification of lesions from 176 to 335 (p<0.001) and chromoendoscopy to 646 (p<0.001). The additional lesions were mainly flat (type IIb, 74%), which were only recognized using i-Scan or chromoendoscopy. The amount of neoplasias was not significantly different (HD+: 5, i-Scan: 11, Chromoendoscopy: 11), but all could correctly be predicted using i-Scan or chromoendoscopy. CONCLUSIONS: HD+ colonoscopy with and without i-Scan unmask a plethora of small lesions but chromoendoscopy can even advance the number. However, i-Scan was able to predict neoplasia as precisely as chromoendoscopy and might shortly replace chromoendoscopy as a more time efficient tool.