Tumore des biliären Trakts: Häufigkeit, Diagnostik und Therapie

Die malignen Tumoren des biliären Trakts, unterteilt in Gallenblasen- und Gallengangskarzinome, sind eher selten. Dennoch wurden in den vergangenen Jahren Fortschritt in Diagnostik und Therapie erzielt. Neben Verbesserung der operativen Techniken als einzige kurative Option konnte auch ein chemotherapeutischer Standard bei fortgeschrittenen Tumoren etabliert werden. Multimodal Konzepte stehen im Fokus des Forschungsinteresses

Humanes Papillomavirus und Analkarzinom: Diagnose, Screening und Therapie

Zusammenfassung: Die Inzidenz des Analkarzinoms nimmt weltweit zu, vor allem bei männlichen homosexuellen Patienten. Als hauptsächlicher Risikofaktor für die Entstehung des Analkarzinoms gilt die anale Infektion mit dem humanen Papillomavirus (HPV). Die Prävalenz der analen HPV-Infektion bei HIV-negativen homosexuellen Männern beträgt 50-60%. Bei HIV-positiven homosexuellen Männern liegt die Prävalenz bei nahezu 100%. Die HPV-assoziierte anale intraepitheliale Neoplasie (AIN) gilt als Vorläuferläsion des Analkarzinoms. Bei etwa 20% der HIV-negativen homosexuellen Männer lässt sich eine AIN diagnostizieren, wobei bei 5-10% eine hochgradige Epitheldysplasie (AINII-III) vorkommt. Die Prävalenz der hochgradigen AIN ist jedoch mit bis zu 50% bei HIV-positiven homosexuellen Patienten bedeutend höher. Trotz der Häufigkeit von HPV-bedingten analen Epitheldysplasien und der zunehmenden Fälle von Analkarzinomen gibt es aber noch immer keinen Konsens bezüglich des Screenings, der Therapie und der Überwachung von Patienten mit AIN. Im Falle eines Analkarzinoms ist unabhängig vom HPV- oder HIV-Status heute noch immer die Radiochemotherapie mit 5-FU und MitomycinC Standar

Stereotaktische Strahlentherapie von Metastasen: Palliativer Effekt und Tumorkontrolle

Zusammenfassung: Hintergrund: Aufgrund längeren Krankheitsverlaufs durch neue Systemtherapien und basierend auf dem Konzept der Oligometastasierung wird in der klinischen Praxis immer häufiger die Indikation für eine lokal definitive Behandlung von Metastasen gestellt. Mit der stereotaktischen Radiotherapie können Metastasen in wenigen Sitzungen effizient abgetötet werden. Fragestellung: Was ist die Evidenz zur stereotaktischen Radiotherapie von Patienten mit Oligometastasen? Wie ist der Einfluss der Metastasenkontrollrate auf das Überleben nach stereotaktischer Radiotherapie? Wie toxisch ist die Behandlung? Wie ist die Abgrenzung von anderen lokalen Therapiemethoden wie z.B. der Chirurgie? Gibt es prognostische Faktoren bei Patienten mit Oligometastasen? Material und Methode: Literatursuche nach prospektiven und retrospektiven Studien. Ergebnisse: Den einzigen Beweis für einen lebensverlängernden Effekt durch lokale Behandlung von Oligometastasen liefert eine randomisierte Studie, die den radiochirurgischen Boost nach Ganzhirnbestrahlung bei Patienten mit Hirnfiliae untersuchte. Prospektive Phase-II-Studien zur stereotaktischen Radiotherapie von Hirn-, Lungen-, Leber-, Wirbelkörper- und Oligometastasen an multiplen Lokalisationen belegen die hohe Tumorkontrollrate und gute Verträglichkeit dieser Behandlung. Prognostische Faktoren sind in erster Linie Histologie, Anzahl und Größe der Metastasen sowie das krankheitsfreie Überleben. Schlussfolgerung: Die stereotaktische Radiotherapie ist eine valide Therapieoption in der Behandlung von Patienten mit Oligometastasen und sollte in der klinischen Praxis auch als Alternative zur Metastasenchirurgie und lokal ablativer Verfahren erwogen werden

Effect of VEGF receptor inhibitor PTK787/ZK222548 combined with ionizing radiation on endothelial cells and tumour growth

The vascular endothelial growth factor (VEGF) receptor is a major target for anti-angiogenesis-based cancer treatment. Here we report the treatment effect of ionizing radiation in combination with the novel orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 on endothelial cell proliferation in vitro and with tumour xenografts in vivo. Combined treatment of human umbilical vein endothelial cells with increasing doses of PTK787/ZK222584 and ionizing radiation abrogated VEGF-dependent proliferation in a dose-dependent way, but inhibition of endothelial cell proliferation was not due to apoptosis induction. In vivo, a combined treatment regimen of PTK787/ZK222584 (4 × 100 mg/kg) during 4 consecutive days in combination with ionizing radiation (4 × 3 Gy) exerted a substantial tumour growth delay for radiation-resistant p53-disfunctional tumour xenografts derived from SW480 colon adenocarcinoma cells while each treatment modality alone had only a minimal effect on tumour size and neovascularization. SW480 tumours from animals that received a combined treatment regimen, displayed not only an extended tumour growth delay but also a significant decrease in the number of microvessels in the tumour xenograft. These results support the model of a cooperative antitumoural effect of angiogenesis inhibitor and irradiation and show that the orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 is suitable for combination therapy with irradiation. © 2001 Cancer Research Campaign http://www.bjcancer.co

Virtually abelian K\"ahler and projective groups

We characterise the virtually abelian groups which are fundamental groups of compact K\"ahler manifolds and of smooth projective varieties. We show that a virtually abelian group is K\"ahler if and only if it is projective. In particular, this allows to describe the K\"ahler condition for such groups in terms of integral symplectic representations

Imexon augments sensitivity of human lymphoma cells to ionizing radiation: in vitro experimental study

BACKGROUND: Imexon is an aziridine-containing small pro-oxidant molecule with promising antitumor activity in myeloma, lymphoma and lung and pancreatic cancer. Imexon is already in clinical trials in patients with advanced solid tumors. The present study examined the effects of imexon on H9 and Raji lymphoma cell lines in vitro when given in combination with ionizing radiation. MATERIALS AND METHODS: H9 and Raji lymphoma cells were grown in culture and exposed to imexon, radiation, or both. Cells were assessed for cell viability, glutathione content, induction of apoptosis, cell cycle distribution and also subject to Western blot analysis. RESULTS: Imexon inhibited cell proliferation in a dose-dependent manner. Imexon, given for 48 h prior to irradiation at a clinically achievable dose of 40 muM, potently enhanced the cell radiosensitivity. Imexon enhanced radiation-induced apoptosis and accumulated cells in G2/M phase of the cell cycle. Imexon induced caspase-3 activation and PARP cleavage. Alterations in glutathione levels were not observed at 40 microM of imexon. CONCLUSION: In conclusion, imexon efficiently augmented lymphoma cell radiosensitivity independently of glutathione and the underlying mechanisms include induction of apoptosis and cell cycle redistribution

Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities

PURPOSE The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA

Late term tolerance in head neck cancer patients irradiated in the IMRT era

BACKGROUND: The aim was to quantify severe transient and persisting late term effects in our single institution head neck cancer (HNC) cohort treated with curatively intended intensity modulated radiation therapy (IMRT). Hypothesis was if a 2-year follow up (FU) is sufficient to estimate the long term tolerance in HNC irradiated in the IMRT era. METHODS: Between 01/2002-8/2012, 707/1211 (58%) consecutively treated IMRT patients met the inclusion criteria of a FU time >12 months and loco-regional disease control (LRC). 45% presented with loco-regionally advanced disease; 55% were referred for curative definitive IMRT (66Gy-72Gy in 30--35 fractions), 45% underwent postoperative IMRT (60-66Gy in 30--33 fractions). Systemic concomitant therapy was administered in 85%. Highly consistent treatment procedures were performed with respect to contouring processes, dose constraints, radiation schedules, and the use of systemic therapy. Grade 3/4 late term effects were prospectively assessed and analyzed with respect to subgroups at particular risk for specific late effects. RESULTS: Mean/median FU of the cohort was 41/35 months (15--124). 13% of the patients (92/707) experienced any grade 3/4 late effects (101 events in 92/707 patients), 81% in the first 12 months after radiation. 4% of all developed persisting late grade 3/4 effects (25 events in 25/707 patients). CONCLUSIONS: IMRT led to a high late term tolerance in loco-regionally disease free HNC patients. The onset of any G3/4 effects showed a plateau at 2 years. The question of the cervical vessel tolerance in disease free long time survivors is still open and currently under evaluation at our institution

Chapter 12: Systematic Review of Prognostic Tests

A number of new biological markers are being studied as predictors of disease or adverse medical events among those who already have a disease. Systematic reviews of this growing literature can help determine whether the available evidence supports use of a new biomarker as a prognostic test that can more accurately place patients into different prognostic groups to improve treatment decisions and the accuracy of outcome predictions. Exemplary reviews of prognostic tests are not widely available, and the methods used to review diagnostic tests do not necessarily address the most important questions about prognostic tests that are used to predict the time-dependent likelihood of future patient outcomes. We provide suggestions for those interested in conducting systematic reviews of a prognostic test. The proposed use of the prognostic test should serve as the framework for a systematic review and to help define the key questions. The outcome probabilities or level of risk and other characteristics of prognostic groups are the most salient statistics for review and perhaps meta-analysis. Reclassification tables can help determine how a prognostic test affects the classification of patients into different prognostic groups, hence their treatment. Review of studies of the association between a potential prognostic test and patient outcomes would have little impact other than to determine whether further development as a prognostic test might be warranted

Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe