Reproducibility of the CROSS Trial Results in the Multimodal Treatment of Esophageal Cancer in Daily Practice: A Single Center Retrospective Observational Study.

Background: Treatment of nonmetastatic esophageal cancer with curative intention remains a major challenge. Neoadjuvant radiochemotherapy followed by surgery, as described in the CROSS trial in 2012, has been established as a standard of care. With this retrospective observational study, we aimed to analyze the results of the CROSS regimen in daily practice over the last 10 years at the St. Clara Hospital, a Swiss center for esophageal surgery. Methods: To determine the clinical outcome in our daily practice, the medical records of all patients with potentially curable localized esophageal cancer (T1N1 or T2-3N0-1 M0) treated with radiochemotherapy in neoadjuvant intention according to the CROSS regimen were reviewed. The primary endpoint was overall survival. Furthermore, an overall survival analysis of the subgroups of patients who exactly met the inclusion criteria of the CROSS trial with respect to age and weight loss before therapy was performed. The Kaplan-Meier method was used to estimate survival and compared by the log-rank test. Results: From January 2012 to January 2022, 91 patients with T1N1 or T2-3N0-1M0 esophageal cancer underwent neoadjuvant radiochemotherapy according to the CROSS regimen. The median age was 70 years (range 31-86 years), and 26 (29%) patients were over 75 years of age. Weight loss of more than 10% was observed in 23 (25%) patients. 77 (85%) patients underwent esophagectomy, and complete resection (R0) was obtained in 73 (95%) of them. The median overall survival was 41 months, compared to 49.4 months in the CROSS trial. The overall survival rate at 12 months was 85% and at 24 months, it was 68%, very similar to the CROSS trial results. 51% of the patients fully met the inclusion criteria of the CROSS trial with respect to age and pretherapeutic weight loss. Their overall survival rate at 12 months was 94% at St. Clara Hospital versus 82% in the CROSS trial (p=0.04), and at 24 months, 81% versus 67% (p=0.05). Conclusion: Overall, in a center specialized for the multimodal treatment of nonmetastatic esophageal cancer, the results of the CROSS trial seem to be well reproducible in daily practice.

Overcoming resistance in a BRAF V600E-mutant adenocarcinoma of the lung.

We report on a patient with an adenocarcinoma of the lung harbouring a BRAF V600E mutation who benefited from combination therapy with dabrafenib-trametinib after developing resistance to vemurafenib. To our knowledge, our report shows, for the first time, that combination therapy with dabrafenib-trametinib can overcome vemurafenib resistance in a BRAF V600E-mutated adenocarcinoma of the lung.

[New therapeutic opportunities in metastatic renal cell carcinoma]. / Neue Therapie-Optionen beim metastasierten Nierenzellkarzinom.

Until recently metastatic renal cell carcinoma was considered refractory to the available therapies. A better understanding of the molecular biology and the introduction of targeted agents led to a significant improvement in the prognosis of patients with metastatic renal cell carcinoma. In this paper the molecular pathology, specifically the deregulation of the oxygen adaption mechanisms leading to tumorangiognesis will be presented. Based on these fundamental mechanisms the targeted agents will be introduced. These agents have been tested in randomized phase III trials in different clinical and prognostic situations. The results and the side-effects of sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab treatment will be presented leading to a possible treatment algorithm.

Magnetization dynamics of Landau structures: tuning the response of mesoscopic magnetic objects using defects.

Magnetic vortex cores are interacting with and can even be annihilated by artificial defects, such as holes. These defects have been fabricated by focused ion beam milling (FIB) into the magnetic domains, domain walls and the center of square-shaped vortices, known as Landau structures. We report the imaging of the magnetization dynamics of Landau structures containing holes by means of x-ray magnetic circular dichroism photo-emission electron microscopy (XMCD-PEEM). Due to the high lateral and temporal resolution of this method, the magnetic excitation spectrum, which is characteristic for the vortex-hole interaction, is investigated in detail. We find that the vortex core as well as domain walls can be trapped by small holes. With the help of micromagnetic simulations we show that the vortex gyrotropic motion frequency is enhanced, whereas the amplitude is significantly reduced in the case of non-centric holes in domain walls.

Dynamic vortex-antivortex interaction in a single cross-tie wall.

A fascinating property of micromagnetism comes from the possibility to control the domain and vortex configuration through the sample shape and size. For instance, in a rectangular platelet a configuration containing a stable combination of vortices and an antivortex can be created. Such a single cross-tie wall can be understood as being a coupled micromagnetic system with three static solitons. Here we report on its magnetization dynamics including the vortex-antivortex interactions. The spectrum of eigenmodes is investigated as well as the effect of different vortex core orientations. We show that the vortex dynamics can be used to identify the core configuration, which is not directly accessible to x-ray microscopy because of its limited spatial resolution.

Time resolved magnetization dynamics of ultrathin Fe(001) films: spin-pumping and two-magnon scattering.

The time-resolved magnetic response of ultrathin epitaxial Fe(001) films grown on GaAs(001) and covered by Au, Pd, and Cr capping layers was investigated by time and spatially resolved Kerr effect measurements. The magnetization was excited by an in-plane magnetic field pulse using the transient internal field generated at a Schottky barrier while the wavelength of the excitation (resonant mode) was roughly 4 microm. Each of the three cap layers affected the spin relaxation in a unique way. Au cap layers resulted in the bulk Gilbert damping of the Fe film. Pd cap layers caused an additional Gilbert damping due to spin-pump or spin-sink effects. Cr cap layers lead to a strong extrinsic damping which can be described by two-magnon scattering. In this case the strength of the extrinsic damping can be controlled by a field induced shift of the spin wave manifold with respect to the excited k vector.

Micromagnetic dissipation, dispersion, and mode conversion in thin permalloy platelets.

Micron-sized ferromagnetic Permalloy disks exhibiting an in-plane ferromagnetic vortex structure are excited by a fast rise time perpendicular magnetic field pulse and their modal structure is analyzed. We find azimuthal and axial modes. By a Fourier filtering technique we can separate and analyze the time dependence of individual modes. Analysis of the experimental data demonstrates that the azimuthal modes damp more quickly than the axial modes. We interpret these results as mode conversion from low-frequency azimuthal modes to the fundamental mode which is higher in frequency, i.e., mode-mode coupling in a system with a single Landau-Lifshitz-Gilbert phenomenological damping constant alpha.

Fourier transform imaging of spin vortex eigenmodes.

Thin-circular lithographically defined magnetic elements with a spin vortex configuration are excited with a short perpendicular magnetic field pulse. We report the first images of excited magnetic eigenmodes up to third order, obtained by means of a phase sensitive Fourier transform imaging technique. Both axially symmetric and symmetry breaking azimuthal eigenmodes are observed. We observe strong oscillations of the magnetization in the central part of the magnetic elements. The experimental data are in good agreement with micromagnetic simulations.

Cutaneous plasmablastic lymphoma in an HIV-positive male: an unrecognized cutaneous manifestation.

Plasmablastic lymphoma (PBL) is a rare and relatively new entity originally described in HIV-infected individuals. This subset of Epstein-Barr-virus (EBV)-related non-Hodgkin lymphomas is now regarded as a distinct clinicopathological category of AIDS-associated lymphomas occurring preferentially in the oral cavity and showing a poor prognosis. We describe for the first time an EBV-associated PBL with an isolated cutaneous distribution on the lower extremities in an HIV-infected heterosexual male and point to the unique clinical, morphological and immunophenotypic characteristics of this lymphoma. The patient presented with fast growing solid and livid nodules on both legs. The large, blastic tumor cells showed the following immunophenotype: CD138+, CD45+, CD20-, CD10-, CD3-, CD30-, bcl-2-, bcl-6-, LMP-1- and EMA-. The proliferation fraction (Mib-1) was >90%. EBV association was demonstrated by in situ hybridization (EBV-encoded RNAs 1/2). Polymerase-chain-reaction-based DNA analysis demonstrated a clonal IgH rearrangement in the absence of a bcl-2/IgH translocation. PBL in HIV patients may occur not only in the oral cavity, but can probably involve any other organs including the skin.

[Primary intraocular lymphoma with unusual clinical presentation and poor outcome]. / Primäres intraokuläres Lymphom mit untypischer Klinik und ungünstigem Verlauf.

BACKGROUND: Primary intraocular lymphoma is a distinct subset of primary non-Hodgkin's lymphoma of the CNS. In general, the primary non-Hodgkin's lymphoma of the CNS is rare, accounting for 1 % of all non-Hodgkin's lymphomas and less than 1 % of all intraocular tumors. HISTORY AND SIGNS: A 70-year-old man was hospitalized in June 2002 because of acute loss of vision on his left eye. A severe vitreous hemorrhage was observed. Ultrasound showed solid subretinal lesions at the posterior fundus. Diagnostic vitreous surgery including a biopsy was performed. An intraocular malignant B-cell lymphoma was determined by immunohistochemistry. General screening revealed no further manifestations of the lymphoma. THERAPY AND OUTCOME: The patient initially refused any therapy until a painful secondary neovascular glaucoma with complete loss of visual function developed, thus prompting us to perform an enucleation. The following immunohistochemical examination confirmed the initial diagnosis. A chemotherapy with high-dose methotrexate and leucovorin rescue was initiated. CONCLUSIONS: Primary intraocular lymphoma can present as diffuse uveitis refractory to corticosteroids. Diagnosis can be difficult and is often delayed.

Ultrafast generation of magnetic fields in a Schottky diode.

For the development of future magnetic data storage technologies, the ultrafast generation of local magnetic fields is essential. Subnanosecond excitation of the magnetic state has so far been achieved by launching current pulses into micro-coils and micro-striplines and by using high-energy electron beams. Local injection of a spin-polarized current through an all-metal junction has been proposed as an efficient method of switching magnetic elements, and experiments seem to confirm this. Spin injection has also been observed in hybrid ferromagnetic-semiconductor structures. Here we introduce a different scheme for the ultrafast generation of local magnetic fields in such a hybrid structure. The basis of our approach is to optically pump a Schottky diode with a focused, approximately 150-fs laser pulse. The laser pulse generates a current across the semiconductor-metal junction, which in turn gives rise to an in-plane magnetic field. This scheme combines the localization of current injection techniques with the speed of current generation at a Schottky barrier. Specific advantages include the ability to rapidly create local fields along any in-plane direction anywhere on the sample, the ability to scan the field over many magnetic elements and the ability to tune the magnitude of the field with the diode bias voltage.

Imaging precessional motion of the magnetization vector.

We report on imaging of three-dimensional precessional orbits of the magnetization vector in a magnetic field by means of a time-resolved vectorial Kerr experiment that measures all three components of the magnetization vector with picosecond resolution. Images of the precessional mode taken with submicrometer spatial resolution reveal that the dynamical excitation in this time regime roughly mirrors the symmetry of the underlying equilibrium spin configuration and that its propagation has a non-wavelike character. These results should form the basis for realistic models of the magnetization dynamics in a largely unexplored but technologically increasingly relevant time scale.

[Iodine-induced hyperthyroidism (iodine-induced Basedow's disease): a current disease picture]. / Die Jod-induzierte Hyperthyreose (Jodbasedow): ein aktuelles Krankheitsbild.

Iodine-induced thyrotoxicosis or "jodbasedow phenomenon" has been reported throughout the world since iodine has been administered to treat endemic goitre. Nowadays, iodinated radiocontrast agents and the antiarrhythmic drug amiodarone are the most common sources of excess iodine load subsequently leading to iodine-induced thyrotoxicosis, especially in elderly patients with underlying goitre. The aim of the study was to identify the number of cases of iodine-induced thyrotoxicosis among patients with thyrotoxicosis in a large urban hospital. Over an 18-month period thyrotoxicosis has been diagnosed in a total of 39 patients. Eight patients with iodine-induced thyrotoxicosis (5 female, 3 male; mean age 60.6 years) have been identified (20%). In all patients with iodine-induced thyrotoxicosis, iodine exposure with a mean iodine dose of 21.5 g was documented 2 to 16 weeks before diagnosis (iodinated radiocontrast agents in 5 patients, amiodarone in 2 patients, kelp tablets in 1 patient). Clinical features were predominantly tachyarrhythmias and heart failure, while 6 of 8 patients had goitre (thyroid volume 31 to 193 ml). Thyroid antibodies were not detected. Diagnosis was confirmed in 5 of 8 patients with increased urinary iodine concentrations (3436 to > 6000 nmol/24 h), and in 3 of 8 patients with a low tracer uptake in thyroid scintigraphy (1 to 4%). Treatment consisted of methimazole in all patients, additional tional beta-blockers and lithium in 4 patients, and prednisone in 5 patients. The mean treatment ment duration was 9.2 months, and patients became euthyroid after a mean treatment duration of 6.4 weeks. One patient (with still elevated free thyroxine levels) died of myocardial infarction 4 weeks after antithyroid drug therapy had been installed. The incidence, mechanisms and features of iodine-induced thyrotoxicosis are discussed. Iodine-induced thyrotoxicosis is a common disease, and the recognition and treatment of iodine-induced thyrotoxicosis, particularly in elderly patients and patients with goitre, are of clinical importance.

Search for oncogenic regulators in an autocrine tumor model using differential display PCR: identification of novel candidate genes including the calcium channel mtrp6.

A hemopoietic multistep tumor model, in which IL-3 dependent PB-3c mast cells, following expression of v-H-ras progress in vivo to IL-3 producing autocrine tumors has previously been established. Central for this oncogenic progression is a recessive step, which is reversible by cell fusion and leads to stabilization of IL-3 mRNA with concomitant activation of the autocrine loop. Comparing the IL-3 dependent PB-3c and the IL-3 autocrine V2D1 tumor cells with differential display PCR revealed 12 differentially expressed genes of which eight were upregulated and four downregulated in the tumor. They included four proteases (mouse mast cell protease 2, granzyme B, pepsinogen F and serine protease 1) and two metabolic enzymes (adenine phosphoribosyltransferase and fructose1,6-bisphosphatase). For validation, expression of the identified genes was tested in independent PB-3c precursor clones and their tumor derivatives. Expression of an endogenous retroviral IAP element and three unknown transcripts were consistently upregulated in all tumor lines. In somatic cell hybrids, two of these unknown cDNAs showed a dominant and one a recessive expression pattern. One transcript, expressed in the precursor but downregulated in the tumor cells, was cloned and identified as the murine calcium channel mtrp6.

Direct identification of differentially expressed genes by cycle sequencing and cycle labelling using the differential display PCR primers.

Differential display PCR (DD-PCR) is an mRNA fingerprinting technique to identify differentially expressed genes by comparative display of arbitrarily amplified cDNA subsets. This attractively simple screening method was, however, followed by a labour intensive multistep identification procedure for DD-PCR products. In this report we demonstrate for the mouse mast cell protease 2 (MMCP-2) and the cytotoxic T-lymphocyte associated gene transcript CTLA-1 a streamlined approach by (i) direct cycle sequencing with the upstream differential display (DD) primer, followed by (ii) the PCR based generation of an antisense northern probe with the downstream anchor primer.

Acoustic ringing effects in pulsed nuclear magnetic resonance probes.

The troublesome spurious ringing phenomenon found in pulsed nuclear magnetic resonance probes is explained in terms of the electromagnetic generation and detection of ultrasonic waves. A few techniques for eliminating this problem are discussed.