[Risk analysis of gastroenterological endoscopies by routine data using the example of endoscopic retrograde cholangio-pancreatography (ERCP)]. / Risikoanalyse gastroenterologischer Endoskopien durch Routinedaten am Beispiel der Endoskopischen Retrograden Cholangio-Pankreaticographie (ERCP).

BACKGROUND: The present study evaluates the analysis of routine data within quality control management by means of ERCP in a tertiary center over five years. METHODS: In a retrospective study, we analyzed pseudonymized routine administrative data according § 21 KHEntgG. These data can be tracked with regard to specific indicators for all hospitals and after data revocation for each individual hospital. Indicators can be selected according to the combination of diagnoses and OPS-numbers. In the present study, the frequency of the combination of ERCP with pancreatitis (nominator) in ratio to ERCP without pancreatitis (denominator) was analyzed at the Helios Clinic Krefeld for the years 2016 to 2020. Data recruitment was done by 3M Germany. Revocation of pseudonymized data was performed by Helios. Data are expressed as absolute values, percentage, mean + SD and range. RESULTS: Overall, 1521 patients and ERCPs with 4981 procedures, including 688 papillotomies, were analyzed. In 30-70% of cases, ERCP was performed during emergency hospitalization. Forty-seven men and 52 women with ERCP-associated pancreatitis and 718 men and 504 women with ERCP without associated pancreatitis were detected. Among these, 99 patients had a combination of ERCP and pancreatitis,Forty-one percent of the patients developed pancreatitis after (n=41) and 59% before the ERCP (n=58). Emergency admission was comparable in both groups (25-83%). All patients developed post-ERCP pancreatitis within 12 hours post intervention. The course of ERCP-induced pancreatitis (n=41) was slight in most of the patients. In 30 patients an edematous, and in 9 patients an exudative pancreatitis developed. In 2 patients, a necrotizing pancreatitis was observed and one patient died. CONCLUSION: The results of our study indicate that the analysis of routine administrative data allows for the simple assessment of the complication rates of elective ERCPs, even with interventions at the naive papilla.

Anatomy of the Eustachian Tube.

The eustachian tube consists of 2 compartments: the Rüdinger's safety canal and the auxiliary gap. It is surrounded by a cartilaginous wall on the craniomedial side and a membranous wall on the inferolateral side. The eustachian tube cartilage is firmly attached to the skull base by the lateral and the medial suspensory ligaments, which are separated by the medial Ostmann fat pad. The function of the isometric tensor veli palatini muscle is modulated by hypomochlia, which have an influence on the muscular force vectors.

First clinical experiences with a direct acoustic cochlear stimulator in comparison to preoperative fitted conventional hearing aids.

OBJECTIVE: Patients with moderate-to-severe mixed hearing losses (MHLs) are hard to provide sufficient benefit with currently available conventional hearing aids. Here, the long-term safety of a direct acoustic cochlear stimulator (DACS) and the effectiveness compared with conventional "high-performance" hearing aids were investigated. STUDY DESIGN: Prospective, within patient reference, nonrandomized, interventional multicenter clinical study performed at these 3 centers: Medical University Hannover, University of Heidelberg, and Helios Hospital Krefeld. PATIENTS AND INTERVENTION: Ten otosclerosis patients with severe-to-profound MHL were preoperatively fitted with state-of-the-art conventional hearing aids (HA). After 2 months of testing conventional HA, 9 of the patients decided to be implanted with a DACS. MAIN OUTCOME MEASURES: Air conduction (AC) and bone conduction (BC) aided and unaided thresholds, speech discrimination before and after implantation and at 3, 6, and 12 months after activation. The subjective benefit was assessed by the Abbreviated Profile of Hearing Aid Benefit (APHAB). RESULTS: Preoperative hearing thresholds were preserved over the 12 month observation time after activation. Average functional gain (0.5-4 kHz) achieved with conventional HA was 47 dB compared with 56 dB with the DACS. Speech-in-noise tests revealed a lower SNR for DACS (3.1 dB) than for the HA (6.6 dB) and patients were more satisfied with the DACS. CONCLUSION: The DACS significantly improved hearing, speech intelligibility, and satisfaction in patients with a severe-to-profound mixed hearing loss and can be considered a safe and useful alternative to conventional hearing aids.

NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer.

NY-CO-58/KIF2C has been identified as a tumor antigen by screening antibody responses in patients with colorectal cancer. However, expression had not consequently been examined, and nothing was known about its ability to induce spontaneous T cell responses, which have been suggested to play a role in the development of colorectal cancer. We analyzed 5 colorectal cancer cell lines, and tumor samples and adjacent healthy tissues from 176 patients with epithelial cancers for the expression of NY-CO-58/KIF2C by RT-PCR and Western Blot. T cell responses of 43 colorectal cancer patients and 35 healthy donors were evaluated by ELISpot following stimulation with 30mer peptides or full-length protein. All cell lines and tumor samples from colorectal cancer patients expressed NY-CO-58/KIF2C on the protein and RNA level, and expression levels correlated strongly with Ki-67 expression (r = 0.69; p = 0.0003). Investigating NY-CO-58/KIF2C-specific T cell responses, CD8(+) T cells directed against 1 or more peptides were found in less than 10% of patients, whereas specific CD4(+) T cells were detected in close to 50% of patients. These T cells were of high avidity, recognized the naturally processed antigen and secreted IFN-gamma and TNF-alpha. Depletion of CD4(+)CD25(+) T cells before stimulation significantly increased the intensity of the preexisting response. NY-CO-58/KIF2C is significantly overexpressed in colorectal and other epithelial cancers and expression levels correlate with the proliferative activity of the tumor. Importantly, NY-CO-58/KIF2C was able to induce spontaneous CD4(+) T cell responses of the Th1-type, which were tightly controlled by peripheral T regulatory cells.

Virtual reality: a new paranasal sinus surgery simulator.

OBJECTIVES/HYPOTHESIS: Virtual surgical training systems are of growing value. Current prototypes for endonasal sinus surgery simulation are very expensive or lack running stability. No reliable system is available to a notable number of users yet. The purpose of this work was to develop a dependable simulator running on standard PC hardware including a detailed anatomic model, realistic tools and handling, stereoscopic view, and force feedback. STUDY DESIGN: Descriptive. METHODS: A three-dimensional voxel model was created based on a high-resolution computed tomography study of a human skull, from which the bony structures were segmented. The mucosa and organs at risk were added manually. The model may be manipulated with virtual surgical tools controlled with a low-cost haptic device, which is also used to adjust microscopic or endoscopic views. Visualization, haptic rendering, and tissue removal are represented with subvoxel resolution. RESULTS: The handling of the model is convincing. The haptic device provides a realistic feeling regarding the interaction between tool tip and anatomy. Three-dimensional orientation and the look and feel of virtual surgical interventions get close to reality. CONCLUSIONS: The newly developed system is a stable, fully operational simulator for sinus surgery based on standard PC hardware. Besides the limitations of a low-cost haptic device, the presented system is highly realistic regarding anatomy, visualization, manipulation, and the appearance of the tools. It is mainly intended for gaining surgical anatomy knowledge and for training navigation in a complex anatomical environment. Learning effects, including motor skills, have yet to be quantified.

Using a virtual reality temporal bone simulator to assess otolaryngology trainees.

OBJECTIVE: The objective of this study is to determine the feasibility of computerized evaluation of resident performance using hand motion analysis on a virtual reality temporal bone (VR TB) simulator. We hypothesized that both computerized analysis and expert ratings would discriminate the performance of novices from experienced trainees. We also hypothesized that performance on the virtual reality temporal bone simulator (VR TB) would differentiate based on previous drilling experience. STUDY DESIGN: The authors conducted a randomized, blind assessment study. METHODS: Nineteen volunteers from the Otolaryngology-Head and Neck Surgery training program at the University of Toronto drilled both a cadaveric TB and a simulated VR TB. Expert reviewers were asked to assess operative readiness of the trainee based on a blind video review of their performance. Computerized hand motion analysis of each participant's performance was conducted. RESULTS: Expert raters were able to discriminate novices from experienced trainees (P < .05) on cadaveric temporal bones, and there was a trend toward discrimination on VR TB performance. Hand motion analysis showed that experienced trainees had better movement economy than novices (P < .05) on the VR TB. CONCLUSION: Performance, as measured by hand motion analysis on the VR TB simulator, reflects trainees' previous drilling experience. This study suggests that otolaryngology trainees could accomplish initial temporal bone training on a VR TB simulator, which can provide feedback to the trainee, and may reduce the need for constant faculty supervision and evaluation.

Expression of cancer-testis antigens as possible targets for antigen-specific immunotherapy in head and neck squamous cell carcinoma.

Cancer-Testis (CT) antigens are by definition expressed in tumor but not in healthy tissue except testis and might represent ideal targets for antigen-specific immunotherapy. Here, we present the first comprehensive analysis of CT antigen expression in patients with head and neck squamous cell carcinoma (HNSCC). Tumor samples (N = 51), and adjacent healthy tissue from patients with HNSCC were analyzed for the expression of 23 genes designated CT antigens using RT-PCR. Patient sera (N = 39) were screened for IgG antibody responses against NY-ESO-1, MAGEA3, and SSX2. According to their expression pattern antigens were divided into four groups. ADAM2, LIP1, SLLP1, AKAP3, CTAGE, ZNF165, CAGE, and FTHL17 were expressed in tumor and healthy tissue at comparable frequencies. NY-TLU-57, GAGE1, SAGE1 were expressed more frequently in tumor samples than in healthy tissues. TPTE, LDHC, SPO11 were expressed neither in tumor samples nor in healthy tissue. 9 CT antigens were expressed only in the tumor tissue and may represent ideal candidates for active immunotherapy in HNSCC: MAGEA3 was expressed in 72%, SSX1 in 45%, MAGEC2 in 33%, MAGEC1 in 28%, BAGE in 17%, SSX2 in 16%, SCP1 in 12%, NY-ESO-1 in 6%, and HOM-TES-85 in 4% of cases. 86% of tumor samples expressed at least one, 69% expressed at least two, and 43% expressed at least three of these antigens. Three patients showed an antibody response against NY-ESO-1. In conclusion, we demonstrate here that HNSCC frequently express CT antigens. Furthermore, a relatively high percentage of tumors express more than one CT antigen opening the perspective for polyvalent antigen-specific immunotherapy.

Pathophysiology of the Eustachian tube--relevant new aspects for the head and neck surgeon.

OBJECTIVES: The impact of cranio-maxillofacial procedures upon Eustachian tube function is still largely unknown. The aim of this presentation is to depict new aspects of Eustachian tube function and to demonstrate its importance to cranio-maxillofacial surgery. METHODS: Two different groups of patients were examined both clinically and by MRI of the Eustachian tube region. One of these groups comprised 15 adult patients with a history of cleft palate; another consisted of 32 patients with a history of a so-called patulous Eustachian tube. RESULTS: Clinical and MRI-findings revealed that the problem of persistent chronic middle ear disease with cleft palate patients depends crucially on the integrity of the pterygoid hamulus and of the tensor veli palatini muscle after cleft palate repair. The masticatory muscles on the other hand also play an important role in Eustachian tube function in non-cleft patients. CONCLUSION: The maxillofacial surgeon should be aware that he holds a key position for preventing as well as treating Eustachian tube pathophysiology.

Computer-based anatomy a prerequisite for computer-assisted radiology and surgery.

RATIONALE AND OBJECTIVES: The aim of the study is to show the possibilities opened up by three-dimensional (3D) computer-based models of the human body for education in anatomy, training of radiological and endoscopic examinations, and simulation of surgical procedures. MATERIALS AND METHODS: Based on 3D data sets obtained from the Visible Human and/or clinical cases, virtual body models are created that provide an integrated spatial and symbolic description of the anatomy by using interactive color/intensity-based segmentation, ray casting visualization with subvoxel resolution, a semantic network for knowledge modeling, and augmented QuickTime VR (Apple Computer, Inc, Cupertino, CA) movies for presentation. RESULTS: From these models, various radiological, endoscopic, or haptic manifestations of the body can be derived. This is shown with examples from anatomy teaching, correlation of x-ray images with 3D anatomy for education in radiology, gastrointestinal endoscopy, correlation of ultrasound images with 3D anatomy in endoscopic ultrasonography, and simulation of drilling in temporal bone surgery. CONCLUSION: The presented models provide a means for realistic training in interpretation of radiological and endoscopic images of the human body. Furthermore, certain surgical procedures may be simulated realistically. Used as a complement to the current curriculum, these models have the potential to greatly decrease education times and costs.

Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness.

KCNQ4 is an M-type K+ channel expressed in sensory hair cells of the inner ear and in the central auditory pathway. KCNQ4 mutations underlie human DFNA2 dominant progressive hearing loss. We now generated mice in which the KCNQ4 gene was disrupted or carried a dominant negative DFNA2 mutation. Although KCNQ4 is strongly expressed in vestibular hair cells, vestibular function appeared normal. Auditory function was only slightly impaired initially. It then declined over several weeks in Kcnq4-/- mice and over several months in mice carrying the dominant negative allele. This progressive hearing loss was paralleled by a selective degeneration of outer hair cells (OHCs). KCNQ4 disruption abolished the I(K,n) current of OHCs. The ensuing depolarization of OHCs impaired sound amplification. Inner hair cells and their afferent synapses remained mostly intact. These cells were only slightly depolarized and showed near-normal presynaptic function. We conclude that the hearing loss in DFNA2 is predominantly caused by a slow degeneration of OHCs resulting from chronic depolarization.

In vitro isolation and cell culture of vestibular inner ear melanocytes.

INTRODUCTION: Melanocytes of the membranous labyrinth of the inner ear have been described morphologically in various contexts. Nature and functions of these cells are as yet not completely clear, even though several hypotheses exist regarding the same. The limited knowledge is due in part to a lack of methods regarding in vitro cell culture. The aim of this study was to describe conditions for the successful cell culture of vestibular inner ear melanocytes (VIEM), to compare their growth properties with those of epidermal melanocytes, and to characterize them immunohistochemically. MATERIALS AND METHODS: Membranous labyrinth cells from freshly slaughtered sheep were isolated, and melanocytes and fibroblasts subsequently cultured. In addition, melanocytes from the skin of the same sheep were cultured. Antibodies specific to tyrosinase, tyrosinase-related protein 1 (TRP-1/Mel-5), and melanoma-specific antigen A (Melan A) were used to analyze the cultured cells. RESULTS: The proliferation of VIEM was retarded in comparison to epidermal melanocytes. After 14 days, VIEM began to proliferate for the first time, whereas epidermal melanocytes proliferated already after 7 days. In contrast to epidermal melanocytes, the culturing process of VIEM seemed to be dependent on the presence of fibroblasts, and VIEM often accumulated in the vicinity of fibroblasts forming three-dimensional clusters. Moreover, VIEM showed a higher ratio of highly pigmented cells with a round cell shape and small dendrites in comparison to epidermal melanocytes. Immunohistochemical techniques proved the VIEM to be positive for Melan A, TRP-1 and, in the majority of cases, also for tyrosinase. CONCLUSION: We successfully cultured melanocytes of the inner ear vestibular labyrinth for the first time and demonstrated melanocytic characteristics of these cells. This accomplishment will provide the opportunity to investigate VIEM in more detail in future experiments.

Laryngeal morphometry with a new laser 'clip on' device.

BACKGROUND AND OBJECTIVES: Qualitative laryngoscopic investigations belong to diagnostic routine in laryngology. Nevertheless, quantitative morphometric measurements of intralaryngeal structures have been difficult by now. STUDY DESIGN/MATERIAL AND METHODS: The development of a two-point-light projection method for endolaryngeal measurements that works with a double reflecting mirror and green laser light is shown. RESULTS: The laser beams that have a distance of exactly 2 mm are very well visible at the surface of laryngeal structures. The technique can be used during a routine videoendoscopic examination. CONCLUSION: In our opinion this method enables accurate quantitative morphological measurement within the larynx that could be used even in clinical routine. The two-point light projection technique helps to reduce former limitations of endoscopic investigations.

Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold.

K-Cl co-transporters are encoded by four homologous genes and may have roles in transepithelial transport and in the regulation of cell volume and cytoplasmic chloride. KCC3, an isoform mutated in the human Anderman syndrome, is expressed in brain, epithelia and other tissues. To investigate the physiological functions of KCC3, we disrupted its gene in mice. This severely impaired cell volume regulation as assessed in renal tubules and neurons, and moderately raised intraneuronal Cl(-) concentration. Kcc3(-/-) mice showed severe motor abnormalities correlating with a progressive neurodegeneration in the peripheral and CNS. Although no spontaneous seizures were observed, Kcc3(-/-) mice displayed reduced seizure threshold and spike-wave complexes on electrocorticograms. These resembled EEG abnormalities in patients with Anderman syndrome. Kcc3(-/-) mice also displayed arterial hypertension and a slowly progressive deafness. KCC3 was expressed in many, but not all cells of the inner ear K(+) recycling pathway. These cells slowly degenerated, as did sensory hair cells. The present mouse model has revealed important cellular and systemic functions of KCC3 and is highly relevant for Anderman syndrome.

The muscular compliance of the auditory tube: a model-based survey.

OBJECTIVES: The role of the paratubal muscles, especially the medial pterygoid muscle, still is unclear. The aim of this study was to define the function of the medial pterygoid muscle concerning the muscular compliance of the auditory tube. METHODS: High-resolution cross-sectional T1 magnetic resonance imaging data of one of the authors' paratubal structures were used, a new functional 3-D model of the auditory tube and its related structures visualized by the Hamburg VOXEL-MAN digital image system. RESULTS: Functional 3-D reconstructions of the paratubal structures reveal that the medial pterygoid muscle is acting as a movable hypomochlion of the tensor veli palatini muscle. Contraction of the medial pterygoid muscle increases and relaxation decreases the force of the tensor veli palatini muscle on the distal part of the auditory tube. Hence, the opening pressure of the auditory tube is moderated by the action of the medial pterygoid muscle. CONCLUSION: The influence of the medial pterygoid muscle on the opening pressure of the auditory tube may have an impact on the diagnosis and therapy in patients with patent auditory tube as well as the middle ear pathology in patients with cleft palate.

Volume cutting for virtual petrous bone surgery.

A profound knowledge of anatomy and surgical landmarks of the temporal bone is a basic necessity for any otologic surgeon. Because this knowledge, so far, has been mostly taught by limited temporal bone drilling courses, our objective was to create a system for virtual petrous bone surgery that allows the realistic simulation of specific laterobasal surgical approaches. A major requirement was the development of an interactive drill-like tool, together with a new technique for realistic visualization of simulated cut surfaces. The system is based on a volumetric, high-resolution model of the temporal bone, derived from CT. Interactive volume cutting methods using a new multivolume scheme have been developed. In this scheme, cut regions are modeled independently in additional data volumes using voxelization techniques. The voxelization is adapted to successive cutting operations as needed for the simulation of a drill-like tool. A new visualization technique was developed for artifact-free rendering of sharp edges, as formed by the intersection of a cut and an object surface. The new multivolume visualization technique allows high-quality visualization of interactively generated cut surfaces. This is a necessity for a realistic simulation of petrous bone surgery. Our system therefore facilitates comprehension of the complex morphology, and enables the recognition of surgical landmarks, which is most important if injury to delicate organs (e.g., the facial nerve or auditory ossicles) is to be avoided. The system for virtual petrous bone surgery allows the simulation of specific surgical approaches with high-quality visualization. The user can learn about the complex three-dimensional anatomy of the temporal bone from the viewpoint of a real otosurgical procedure.