Frameless linac-based (Novalis TX) stereotactic treatment for vestibular schwannoma that extend distally into the iac (Internal Acoustic Canal): an analysis of the dose to the cochlea

Objectives: We compare the dose parameters between 3 different radiosurgery delivery techniques which may have an impact on cochlea function. Methods: Five patients with unilateral vestibular schwannoma (VS) were selected for this study. Planning procedure was carried out using the BrainLAB® iPlan planning system v. 4.5. For each patient three different planning techniques were used: dynamic arc (DA) with 5 arcs per plan, hybrid arc (HA) with 5 arcs per plan and IMRT with 8 fields per plan. For each technique, two plans were generated with different methods: with the first method (PTV coverage) it was the goal to fully cover the PTV with at least 12 Gy (normalization: 12 Gy covered 99% of the PTV) and with the second method (cochlea sparing) it was the goal to spare the cochlea (normalization: 12 Gy covers 50% of the PTV/V4Gy of cochlea lower than 1%). Plan evaluation was done considering target volume and coverage (conformity and homogeneity) and OAR constraints (mean (Dmean) and maximum dose (Dmax) to cochlea, Dmax to brainstem and cochlea). The total number of monitor units (MU) was analyzed. Results: The median tumor volume was 0.95 cm³ (range, 0.86-3 cm³). The median PTV was 1.44 cm³ (range, 1-3.5 cm³). The median distance between the tumor and the cochlea's modiulus was 2.7 mm (range, 1.8-6.3 mm). For the PTV coverage method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.872) and in Dmean (p= 0.860). We found a significant correlation (p< 0.05) between the target volume and the cochlear Dmean for all plans with Pearson's coefficient correlation of 0.90, 0.92 and 0.94 for the DA, HA and IMRT techniques, respectively. For the cochlea sparing method, when we compared the cochlear dose in VS patients planned with DA, HA and IMRT, there were no significant differences in Dmax (p = 0.310) and in Dmean (p= 0.275). However, in this group the V4Gy of the ipsilateral cochlea represents less than 1%. When using the HA or IMRT technique, the homogeneity and conformity in the PTV, but also the number of MUs were increased in comparison to the DA technique. Conclusion: VS tumors that extend distally into the IAC had an equivalent sparing of cochlea with DA approach compared with the HA and IMRT techniques. Disclosure: No significant relationships.

Clinical features and practical diagnosis of bullous pemphigoid

Bullous pemphigoid (BP) represents the most common autoimmune subepidermal blistering disease. BP typically affects the elderly and is associated with significant morbidity. It has usually a chronic course with spontaneous exacerbations. The cutaneous manifestations of BP can be extremely protean. While diagnosis of BP in the bullous stage is straightforward, in the non-bullous stage or in atypical variants of BP signs and symptoms are frequently non-specific with eg, only itchy excoriated, eczematous, papular and/or urticarial lesions that may persist for several weeks or months. Diagnosis of BP critically relies on immunopathologic examinations including direct immunofluorescence microscopy and detection of serum autoantibodies by indirect immunofluorescence microscopy or BP180-ELISA.

Novel approaches to therapy of hypereosinophilic syndromes

There has been recent progress in the understanding of the pathogenesis of the hypereosinophilic syndromes (HES). This led to the distinction of subgroups, in which the underlying cause has been identified. Consequently, new treatment options became available, such as imatinib and mepolizumab, which proved to be promising. This article summarizes these new pharmacologic approaches to the therapy of HES.

The basophil activation test in immediate-type drug allergy

Diagnosis of drug allergy involves first the recognition of sometimes unusual symptoms as drug allergy and, second, the identification of the eliciting drug. This is an often difficult task, as the clinical picture and underlying pathomechanisms are heterogeneous. In clinical routine, physicians frequently have to rely upon a suggestive history and eventual provocation tests, both having their specific limitations. For this reason both in vivo (skin tests) and in vitro tests are investigated intensively as tools to identify the disease-eliciting drug. One of the tests evaluated in drug allergy is the basophil activation test (BAT). Basophils with their high-affinity IgE receptors are easily accessible and therefore can be used as indicator cells for IgE-mediated reactions. Upon allergen challenge and cross-linking of membrane-bound IgE antibodies (via Fc-epsilon-RI) basophils up-regulate certain activation markers on their surface such as CD63 and CD203c, as well as intracellular markers (eg, phosphorylated p38MAPK). In BAT, these alterations can be detected rapidly on a single-cell basis by multicolor flow cytometry using specific monoclonal antibodies. Combining this technique with in vitro passive sensitization of donor basophils with patients' serum, one can prove the IgE dependence of a drug reaction. This article summarizes the authors' current experience with the BAT in the diagnostic management of immediate-type drug allergy mediated by drug-specific IgE antibodies.

In vitro tests in drug hypersensitivity diagnosis

The diagnosis of a drug hypersensitivity reaction (DHR) is a challenging task because multiple and complex mechanisms are involved. Better understanding of immunologic pathomechanisms in DHRs and rapid progress in cellular-based in-vitro tests can help to adjust the correct diagnostic strategy to individual patients with different clinical manifestations of drug allergy. Thus, drug hypersensitivity diagnosis needs to rely on a combination of medical history and different in vivo and in vitro tests. In this article, the authors discuss current in vitro techniques, most recent findings, and new promising tools in the diagnosis of T-cell-mediated drug hypersensitivity.

Approach to the patient with drug allergy

Drug allergies are adverse drug reactions mediated by the specific immune system. Despite characteristic signs (eg, skin rash) that raise awareness for possible drug allergies, they are great imitators of disease and may hide behind unexpected symptoms. No single standardized diagnostic test can confirm the immune-mediated mechanism or identify the causative drug; therefore, immune-mediated drug hypersensitivity reactions and their causative drugs must be recognized by the constellation of exposure, timing, and clinical features including the pattern of organ manifestation. Additional allergologic investigations (skin tests, in vitro tests, provocation tests) may provide help in identifying the possible eliciting drug.

Vorwort

Die Beiträge des vorliegenden Bandes sind in einer doppelten Weise mit Manfred G. Schmidt verbunden. Sie wurden von Schülern oder von wissenschaftlichen Weggefährten verfasst und sie beziehen sich inhaltlich auf sein Werk. Die thematische Breite der Beiträge entspricht der Breite seines Werkes: Die Aufsätze analysieren Staatstätigkeiten –Wirtschafts-, Sozial- und Bildungspolitiken --, sie untersuchen Parteien, Institutionen, Demokratien und Autokratien, sie beantworten theoretisch-konzeptuelle oder empirische Fragen, sie nutzen die vergleichende Methode oder liefern einen Beitrag zum Verständnis des politischen Systems Deutschlands und sie sprengen engere Fachgrenzen, indem sie wissenschaftliche Kontexte und praktische Folgen von politikwissenschaftlicher Forschung und Lehre thematisieren. Zu all’ diesen Themen hat Manfred Schmidt wichtige Beiträge geliefert. Es war ein Vergnügen diese Festschrift zusammenzustellen. Die schwerste Entscheidung betraf die anzufragenden Kolleginnen und Kollegen. Einfach war die Identifikation von Kollegen am Heidelberger Institut, die besonders eng mit Manfred Schmidt zusammengearbeitet haben und von Schülern und von ihm geprägten Wissenschaftlern, die heute politikwissenschaftliche Professuren innehaben oder auf dem Weg dorthin sind. Bei der Auswahl von Autoren aus dem großen Kreis der Doktoranden spielten auch der Zufall und die Erreichbarkeit eine Rolle. Besonders schwierig war es, die Zahl der etablierten Forscher und Forscherinnen zu limitieren, die das Werk von Manfred G. Schmidt besonders schätzen und mit ihm in verschiedenen Funktionen wissenschaftlich verbunden waren. Mit guten Gründen hätte ich noch viele andere Kolleginnen und Kollegen anfragen können. Nur die Begrenzung des Seitenumfangs hat mich daran gehindert. Daraus wird auch schon deutlich, dass es keineswegs schwierig war, die Autoren zu gewinnen. Für viele war es eine Freude und Ehre an diesem Band mitzuwirken. Ich bedanke mich ganz herzlichen bei allen, die so engagiert zu diesem Projekt beigetragen haben. Frank Castles hat sich Zeit genommen, mit mir auf dem Krindenhof oberhalb des Thunersees die Konzeption des Bandes zu diskutieren; Dietmar Braun, Wolfgang Merkel und Ferdinand Müller-Rommel und viele andere Kollegen standen jederzeit mit Rat und Tat zur Verfügung. Ein besonderer Dank geht an die Mitarbeiterinnen und Mitarbeiter meiner Arbeitsgruppe – allen voran David Weisstanner und Monique Stoll – die in vielen Stunden mühevoller und konzentrierter Arbeit Korrekturen in die Manuskripte übertrugen, die Literaturlisten überprüften und anglichen sowie Tabellen und Graphiken standardisierten. Manfred Schmidts Heidelberger Sekretärin, Ingeborg Zimmermann, begleitete und unterstützte die Arbeiten aufmerksam und mit Feuereifer. Klaus Armingeon im Januar 2013.