StratomeX: Visual Analysis of Large-Scale Heterogeneous Genomics Data for Cancer Subtype Characterization.

Identification and characterization of cancer subtypes are important areas of research that are based on the integrated analysis of multiple heterogeneous genomics datasets. Since there are no tools supporting this process, much of this work is done using ad-hoc scripts and static plots, which is inefficient and limits visual exploration of the data. To address this, we have developed StratomeX, an integrative visualization tool that allows investigators to explore the relationships of candidate subtypes across multiple genomic data types such as gene expression, DNA methylation, or copy number data. StratomeX represents datasets as columns and subtypes as bricks in these columns. Ribbons between the columns connect bricks to show subtype relationships across datasets. Drill-down features enable detailed exploration. StratomeX provides insights into the functional and clinical implications of candidate subtypes by employing small multiples, which allow investigators to assess the effect of subtypes on molecular pathways or outcomes such as patient survival. As the configuration of viewing parameters in such a multi-dataset, multi-view scenario is complex, we propose a meta visualization and configuration interface for dataset dependencies and data-view relationships. StratomeX is developed in close collaboration with domain experts. We describe case studies that illustrate how investigators used the tool to explore subtypes in large datasets and demonstrate how they efficiently replicated findings from the literature and gained new insights into the data.

Point-Based Visualization for Large Hierarchies.

Space-filling layout techniques for tree representations are frequently used when the available screen space is small or the data set is large. In this paper, we propose an efficient approach to space-filling tree representations that uses mechanisms from the point-based rendering paradigm. We present helpful interaction techniques and visual cues that tie in with our layout. Additionally, we relate this new layout approach to common layout mechanisms and evaluate the new layout along the lines of a numerical evaluation using the measures of the Ink-Paper Ratio and overplotted%, and in a preliminary user study. The flexibility of the general approach is illustrated by several enhancements of the basic layout, as well as its usage within the context of two software frameworks from different application fields.

The Design Space of Implicit Hierarchy Visualization: A Survey.

Apart from explicit node-link representations, implicit visualizations and especially the Treemap as their frontrunner have acquired a solid position among the available techniques to visualize hierarchies. Their advantage is a highly space-efficient graphical representation that does not require explicit drawing of edges. In this paper, we survey the design space for this class of visualization techniques. We establish the design space along the four axes of dimensionality, edge representation, node representation, and layout by examining existing implicit hierarchy visualization techniques. The survey is completed by casting some light into regions of the design space that have not yet been explored. Our design space is not a mere theoretical construct, but a practically usable tool for rapid visualization development. To that end, we discuss a software implementation of the introduced design space.

Endoscopy in Barrett's oesophagus: adherence to standards and neoplasia detection in the community practice versus hospital setting.

OBJECTIVE: Potential process differences between hospital and community-based endoscopy for Barrett's oesophagus have not been examined. We aimed at comparing adherence to guidelines and neoplasia detection rates in medical centres (MC) and community practices (CP). DESIGN: Retrospective analysis. SETTING: All histologically confirmed Barrett cases seen over a 3-year period in six MC and 19 CP covering a third of all upper gastrointestinal endoscopies (n = 126,000) performed annually in Berlin, Germany. MAIN OUTCOME MEASURE: Rate of relevant neoplasia (high-grade intraepithelial neoplasia or more) in both settings in relation to adherence to standards. RESULTS: Of 1317 Barrett cases, 66% were seen in CP. CP patients had a shorter mean Barrett length (2.6 cm vs. 3.8 cm; P < 0.001) with fewer biopsies taken during an examination (2.5 vs. 4.1 for Barrett length

Replacement of conventional glucocorticoids by oral pH-modified release budesonide in active and inactive Crohn's disease: results of an open, prospective, multicenter trial.

Glucocorticosteroids (GCS) are established in the treatment of active Crohn's ileitis and ileocolitis. Recently, the topical steroid budesonide was found to be effective in untreated patients with Crohn's disease (CD) causing less side effects than conventional GCS. No clinical data have been reported about the effects of switching from conventional GCS to budesonide in terms of side effects and disease activity. The primary aim of this study was to evaluate the development of side effects after switching from conventional GCS treatment to Eudragit L-coated budesonide (pH-modified release formulation) in patients taking 5-30 mg prednisolone equivalent per day for at least two weeks. In all, 178 patients with active CD (N = 88) or CD in remission during GCS treatment (N = 90) were included. Conventional GCS treatment was tapered down during a maximum of three weeks, with simultaneous intake of 3 x 3 mg budesonide. Thereafter, patients received 3 x 3 mg budesonide alone for six weeks. GCS-related side effects, disease activity and adverse events were documented at study entry and after 0, 2, 4, and 6 weeks of budesonide treatment. The percentage of patients with GCS-related side effects decreased from 65.2% (intention-to-treat-population) at entry to 43.3% (P < 0.0001) at the end of the trial. The total number of GCS-related side effects decreased significantly from 269 to 90. Of the patients who entered the study with active disease under conventional GCS therapy, 38.6% were in remission at the end of the study. Of the patients who entered the study with CD in remission, 78% stayed in remission after switching from conventinal GCS to budesonide. In conclusion, switching from conventional GCS treatment to budesonide leads to a significant reduction of GCS related side effects in patients with CD without causing rapid deterioration of the disease.

Do conventional cleaning and disinfection techniques avoid the risk of endoscopic Helicobacter pylori transmission?

BACKGROUND AND STUDY AIMS: The aim of the present study was to determine whether endoscopes serve as a reservoir for Helicobacter pylori and whether the disinfection technique currently recommended for manual cleaning and disinfection of the instruments completely removes the risk of H. pylori transmission. PATIENTS AND METHODS: A prospective study was carried out in 400 patients who were undergoing upper gastrointestinal endoscopy for routine clinical indications. The patients' H. pylori status of the patients was identified using a urea detection system (HUT) and culture. H. pylori contamination was assayed by culturing rinsing samples from the endoscopes before and after manual cleaning and disinfection. Gastric biopsies were assayed using rapid urease testing (Helicobacter urease test, HUT) of two antral and gastric body biopsies and cultures. RESULTS: A total of 128 of the 400 patients examined were found to be H. pylori-positive using HUT testing. Endoscopes were contaminated in 54 of the 128 rinsing samples from endoscopes used in H. pylori-positive patients (42 %) before cleaning and disinfection. One of the 128 rinsing samples (0.8 %) was found to be contaminated with H. pylori even after routine manual cleaning and disinfection - indicating that these cleaning and disinfection procedures may be insufficient to eradicate H. pylori from endoscopes completely. No seroconversion was observed during serological follow-up in the patient who had previously been examined with an endoscope contaminated with H. pylori. The patient was still found to be seronegative 5 months after inoculation. CONCLUSIONS: Endoscopes are frequently contaminated with H. pylori immediately after gastroduodenal endoscopy in H. pylori-infected patients. Iatrogenic transmission is possible, as H. pylori can survive manual cleaning and disinfection with 2 % glutaraldehyde, particularly when there is ineffective cleaning before disinfection.

Laser disintegration of cyanoacrylate clot with successful endoscopic removal of sclerotherapy needle from gastric varix.

Intravariceal cyanoacrylate injection is a highly effective and safe procedure for the treatment of bleeding gastric varices. Nevertheless, some cases of severe cyanoacrylate-specific complications due to embolization have been described. Technical difficulties, including risk of sclerotherapy needle clogging, and cyanoacrylate sticking to the tip and the accessory channel of the endoscope, have been mentioned in other reports. We report a case in which a sclerotherapy needle that remained stuck in gastric valves after bucrylate injection was successfully removed by laser disintegration of the cyanoacrylate clot.

[Askin's tumor--a rare entity. Case report with references to the literature]. / Der Askin-Tumor--eine Rarität. Ein Fallbericht mit Einflüssen der Literatur.

Askin's Tumour (synonym: primitive neuroectodermal tumour) is a rare neoplasm of the chest wall. In 1979 Askin and Rosai described an unique clinicopathological entity, characterised as a malignant small-cell tumour of the soft tissues of the chest wall in childhood and adolescence. We report on a case of a 28-year old male who had a massive tumour in the left thorax with association to the chest wall. The clinical symptoms were dyspnoea and increasing chest pain. The tumour was revealed as a sarcoma of the lung by CT-guided fine needle aspiration. A pneumectomy of the left lung with partial resection of ribs IV. and V. was performed. Postoperative histology revealed an Askin's tumour of the chest wall with infiltration of the lung. After surgical treatment in our hospital we transferred the patient to an oncological centre for adjuvant chemotherapy. As a consequence of aggressive growth of tumour therapy should be performed in oncological centres in clinical studies. The treatment includes radical surgical resection, neoadjuvant and adjuvant chemotherapy plus radiation. In our case the primary resection was performed because of increasing symptoms. It is difficult to establish an accurate preoperative diagnosis of Askin's tumour. Microscopy and immunohistological stain of the specific marker--neuron-specific enolase--are essential. Multimodal treatment allows a long-term survival, but often the prognosis is infaust.

[Interventional procedures of the bile duct in patients after stomach resections (Billroth II)]. / Interventionelle Eingriffe am Gallengang bei Patienten nach Magenresektionen (Billroth II).

In the hands of an experienced endoscopist ERCP is an important method for the diagnosis of biliopancreatic diseases of Billroth II patients, but less effective than in nonoperated patients. Percutaneous procedures increase the success rate of nonoperative therapy. We report our own results of in 386 Billroth II patients: Success rate of diagnostic ERCP was 73.6% (284/386). Interventional endoscopy was performed in 192 patients: Successful EST was carried out in 93.6% (160/171), and complete extraction of bile duct stones was achieved in 74.8% (107/143), sufficient bile drainage was achieved by placement of transpapillary endoprostheses in 96.3% (79/82), while successful PTCD and percutaneous therapy were performed in 21 cases. Technical problems result from a long afferent loop, the upside-down position in the duodenal stump and difficult bile duct anatomy. We observed a complications rate of 3.6% (14/386) and a mortality of 0.5% (2/386). Our results are comparable with those in the literature, in which a similar number of difficult patients are included.

A new oscillating saw for robotic aided surgery.

In this paper a brief description of a computer and robotic aided surgery system is given with a detailed overview of the necessity to develop special tools for robotic surgery. The application range of this robotic system has been specially focused on the orthopaedics field and, more particularly, on the execution of osteotomies. It was therefore necessary to develop a new saw device which would meet medical and--from the robot system point of view--mechanical as well as functional requirements. After describing the device which was developed on the basis of these requirements, a detailed comparative study of off-the-shelf oscillating saws and the new device is given at the end of the paper.

Intraoperative guidance in maxillofacial and craniofacial surgery.

The authors' experiences with intraoperative computer assisted guidance in interventions in oromaxillofacial and craniofacial surgery are reported. The guidance system SPOCS (Surgical Planning and Orientation Computer Systems, Aesculap, Germany) consists of an infrared light emitting system of diodes and camera, an imaging workstation and assorted freehand instruments. The software is an updated version of the well-known Viewing Wand software (ISG Technologies, Canada). In tests on phantoms, the system proved a mean accuracy of less than 1.5 mm. Within the last 15 clinical tests, the system has achieved an accuracy better than 3 mm which, at the moment, the authors estimate to be sufficient to proceed with its clinical evaluation. Using bone screws to register the patient's position, an accuracy in the range of less than 2 mm in relation to bony reference points has been achieved. By visualizing the tip of the instrument in real time, this technique allows surgical interventions, even in anatomically complicated situations, without endangering vital neighbouring structures. The 'offset' function of the software, by which the surgeon can elongate the tip of the instrument virtually, allows the surgeon to analyse structures before they are penetrated by the instrument as in a 'look ahead' operation. The authors expect computer assisted simulation and guidance systems to improve surgical quality and reduce the risks associated with surgical interventions.

Oral pH-modified release budesonide versus 6-methylprednisolone in active Crohn's disease. German/Austrian Budesonide Study Group.

OBJECTIVE: Corticosteroids are effective in acute Crohn's disease (CD). The present study assessed the effectiveness and safety of oral pH-modified release budesonide (BUD) in patients with active CD in comparison with 6-methylprednisolone (MPred). DESIGN: This was a prospective multicentre, randomized, double-blind, double-dummy study. METHODS: A total of 67 patients with active CD (CDAI > 150) were included. Patients were treated with 3 x 3 mg BUD (n = 34) or MPred (n = 33) according to a weekly tapering schedule (48-32-24-20-16-12-8 mg). The primary aim was remission of CD (CDAI < 150 and decrease by at least 60 points from baseline) after eight weeks. RESULTS: Baseline demographics, disease activity and localization of CD in the small bowel and the colon were similar in both treatment groups. On an intention-to-treat basis 19/34 patients in the BUD group (55.9%) and 24/33 patients in the MPred group (72.7%) were in remission after eight weeks (P = 0.237). Therapy failed in 15/34 patients (44.1%) of the BUD group and in 9/33 patients (27.3%) of the MPred group. The mean CDAI decreased from 262 +/- 50 to 118 +/- 69 in the BUD-group and from 262 +/- 81 to 95 +/- 61 in the Mored group (P = 0.183, final CDAI BUD vs. MPred). Steroid-related side effects appeared in 28.6% of the patients in the BUD group and in 69.7% of the patients in the Mored group (P = 0.0015). CONCLUSIONS: Oral pH-modified release budesonide (3 x 3 mg/day) is almost as effective as a conventional corticosteroid in patients with active CD but causes significantly less corticosteroid-related side effects.

Protective effects of hydroxyethyl starch-deferoxamine in early sepsis.

The protective effects of hydroxyethyl starch-conjugated deferoxamine (HES-DFO), a macromolecular iron chelator, on the initial pathophysiological cascade in septic shock were evaluated following cecal ligation puncture (CLP) in rats. Animals were given an intravenous dose of 3.0 mL of either vehicle (HES) or HES-DFO immediately following completion of the CLP procedure. Animals were sacrificed 30, 60, 120, and 240 min following CLP, and samples of lung, kidney, bowel, and liver were collected for subsequent analysis of glutathione, myeloperoxidase, and evidence for lipid peroxidation based on measurement of thiobarbituric acid reactive substances and conjugated dienes. In addition, the endotoxin levels were determined in the plasma and histomorphological examination was conducted on tissue samples collected at each time point. At almost all time points, a reduction in lipid peroxidation was noted in the HES-DFO-treated rats (p < .05). Glutathione and myoloperoxidase levels were less affected. Lung tissue from animals receiving HEs demonstrated marked microatelectases, septal destruction, and splicing of basal membranes, which were greatly attenuated in animals having received HES-DFO. Similarly, tubulotoxic and mitochondrial damages observed in kidney samples from HES-treated animals were noticeably reduced in the animals having received the chelator. Liver and gut samples demonstrated unspecific inflammatory injury in both groups of animals. In summary, oxygen radical-mediated tissue damage occurs rapidly following CLP-induced sepsis. Based on histological and biochemical endpoints, treatment with the polymeric iron chelator, HES-DFO, significantly attenuates systemic oxidant injury, the degree of protection being most impressive in the lung and kidney.

[Lesions of the pancreatic duct epithelium and histogenesis of exocrine pancreatic carcinomas]. / Pankreasgangepithelläsionen und Histogenese des exokrinen Pankreaskarzinoms.

The bad prognosis of exocrine pancreas carcinoma manifests itself by a high incidence of recidivation, early metastasis formation and a low 5-year survival rate of 1-2% on an average has not essentially been improved in recent times although progress is evident in diagnosis as well as in surgical, radiological and cytostatic therapy. The unfavourable course of illnesses is due to the symptomless early phase rather than the existing diagnostic potential. Thus, a recording, standardization and definition of pancreatic duct atypias is a necessity for optimizing the pattern of examinations. Topographically, the structure of pancreatic parenchyma may be classified by 1) interlobular ducts; 2) intralobular ducts; 3) intercalated ducts; 4) centroacinar cells, and 5) acinar cells. Based on this matrix, entities of varying diagnostic relevance may be derived, i.e. 1) orthological histiomorphological tissue formations; 2) hyperplastic epithelial changes; 3) metaplastic epithelial formations; and 4) atypical hyperplasias. Beyond this, there are numerous indications of a redifferentiation of numerous pancreatic cell types, primarily of acinar cells. The close relationships between ductal and acinar cells may be subsumed as a terminal ductulo-acinar intercalated duct complex. Against the background of chronic pancreatitis and corresponding length of history (< 6.5 years), cancer may develop in up to 16% of cases. On the molecularbiological level, point mutations of the K-ras gene, a mutation or deletion of the p53 suppressor gene and an excess production of the c-erbB-2 protooncogene are found in a great number of pancreatic carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Measuring of AgNORs using image analysis.

A method is presented for the measurement of AgNORs in histological section using an image analysis system. Measurements are performed at the highest magnification (objective 100x) using a CCD camera. In the first step the AgNORs are segmented, counted and measured. In the second step the AgNOR clusters are segmented. Several features for the description of the AgNORs, the AgNOR clusters and their spatial distribution throughout the nucleus are given. As an internal reference, lymphocytes are used and the size features are given relative to the mean size of AgNORs in the lymphocytes. The reproducibility of the features was tested on a series of astrocytomas. This should be carried out with at least 150 tumor cells and 20 reference cells in order for accurate measurements.

[Neuroendocrine system and its tumors]. / Neuroendokrines System mit seinen Tumoren.

The original classification of neuroendocrine tumours proposed by Pearse was based on a common embryologic origin in the neuroectoderm. The term, carcinoid, literally means carcinoma-like, was coined in 1907 to describe the histologic similarity of these tumors to carcinomas on the one hand and their generally indolent biologic behaviour on the other hand. Neuroendocrine tumours represent a group with complex biological, histological, ultrastructural and immunocytochemical properties. This concept was replaced by another classification based on results of modern techniques (electron microscopy, immunocytochemistry, molecular and DNA analyses). This permits a more reliable classification of tumours, that can be used to determine their biological behaviour and prognosis.