Vergleich und Verlauf von Recurrensparesen nach subtotaler Strumaresektion, Hemithyreoidektomie und Thyreoidektomie:eine retrospektive Studie

Die Schilddrüsenoperation ist eine operative Therapie, welche seit dem Jahr 1800 erstmalig von Hedenus erfolgreich mit Heilung angewandt wurde. Charakteristische Folgeerscheinungen sind z.B. Recurrensparesen und Calciumstoffwechselstörungen. In der Literatur werden sehr unterschiedliche Prozentsätze an postoperativen Komplikationen angegeben. Dies betrifft in besonderem Maße die Recurrensparesen. Internationale Studien haben als Ergebnisse Schwankungsbreiten von bis zu 20% gebracht. Um die Effektivität und Sicherheit der in der Raphaelsklinik Münster / Westfalen durchgeführten Operationen in einer klinischen Studie zu verifizieren, sind die beiden Operationsjahrgänge 1999 und 2000 komplett aufgearbeitet worden. Die nachfolgende Arbeit beschäftigt sich im speziellen mit dem Vergleich und Verlauf von Recurrensparesen der verschiedenen Operationsverfahren bei einer mittleren Beobachtungszeit von 48 bzw. 36 Monaten

Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia

Background: Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhibited by hyperthermia, thereby inducing synthetic lethal conditions in every tumor type. Since cisplatin is successfully used combined with hyperthermia (thermochemotherapy), we investigated the effectiveness of combining PARP1-i with thermochemotherapy. Results: The in vitro data demonstrate a decreased in cell survival after addition of PARP1-i to thermochemotherapy, which can be explained by increased DNA damage induction and less DSB repair. These in vitro findings are in line with in vivo model, in which a decreased tumor growth is observed upon addition of PARP1-i. Materials and Methods: Survival of three HR-proficient cell lines after cisplatin, hyperthermia and/or PARP1-i was studied. Cell cycle analyses, quantification of γ-H2AX foci and apoptotic assays were performed to understand these survival data. The effects of treatments were further evaluated by monitoring tumor responses in an in vivo rat model. Conclusions: Our results in HR-proficient cell lines suggest that PARP1-i combined with thermochemotherapy can be a promising clinical approach for all tumors independent of HR status

Sensitizing thermochemotherapy with a PARP1-inhibitor

Cis-diamminedichloroplatinum(II) (cisplatin, cDDP) is an effective chemotherapeutic agent that induces DNA double strand breaks (DSBs), primarily in replicating cells. Generally, such DSBs can be repaired by the classical or backup non-homologous end joining (c-NHEJ/b-NHEJ) or homologous recombination (HR). Therefore, inhibiting these pathways in cancer cells should enhance the efficiency of cDDP treatments. Indeed, inhibition of HR by hyperthermia (HT) sensitizes cancer cells to cDDP and in the Netherlands this combination is a standard treatment option for recurrent cervical cancer after previous radiotherapy. Additionally, cDDP has been demonstrated to disrupt c-NHEJ, which likely further increases the treatment efficacy. However, if one of these pathways is blocked, DSB repair functions can be sustained by the Poly-(ADP-ribose)-polymerase1 (PARP1)-dependent b-NHEJ. Therefore, disabling b-NHEJ should, in principle, further inhibit the repair of cDDP-induced DNA lesions and enhance the toxicity of thermochemotherapy. To explore this hypothesis, we treated a panel of cancer cell lines with HT, cDDP and a PARP1-i and measured various end-point relevant in cancer treatment. Our results demonstrate that PARP1-i does not considerably increase the efficacy of HT combined with standard, commonly used cDDP concentrations. However, in the presence of a PARP1-i, ten-fold lower concentration of cDDP can be used to induce similar cytotoxic effects. PARP1 inhibition may thus permit a substantial lowering of cDDP concentrations without diminishing treatment efficacy, potentially reducing systemic side effects

Kimmeridgian-Tithonian sea-level fluctuations in the Uljanovsk-Saratov Basin (Russian Platform)

Abstract The Uljanovsk-Saratov Basin, located in the southeast of the Russian Platform, presents an intriguing record of the Kimmeridgian-Tithonian sea-level fluctuations. In the Late Jurassic, this basin was a trough within the Interior Russian Sea. The data available from both outcrops and boreholes have permitted outlining a number of lithostratigraphic units and regional hiatuses in the northeastern segment of the Uljanovsk-Saratov Basin, thus permitting a precise reconstruction of transgressions/regressions and deepenings/shallowings. In total, three transgressive-regressive cycles and two deepening pulses have been established. These regionally documented changes were both related in part to global eustatic changes, and they also corresponded in part to the regional sea-level changes in some basins of Western Europe and Northern Africa, but not to those of the Arabian Platform. Differences observed between the global and regional curves as well as rapid Tithonian sea-level oscillations are explained by the influences of tectonic activity. It is hypothesized that the regional Tithonian oxygen depletion might have been a consequence from the rapid flooding of a densely vegetated land

ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

New Creation instead of new Exodus : the innerbiblical exegesis and theological transformations of Isaiah 65:17–25

akzeptierte Manuskriptversio

Full-dose cisplatin chemotherapy combined with hemodialysis in a patient with impaired renal function and a mediastinal germ cell tumor

Contains fulltext : 229154.pdf (Publisher’s version ) (Closed access)Cisplatin is the first choice treatment in mediastinal germ cell tumors. However, concerns regarding increased toxicity of cisplatin hamper its administration in patients with impaired renal function. We describe a 42-year-old man with chronic kidney disease stage 4 who was diagnosed with a mediastinal germ cell tumor and metastases in lung and brain. Treatment with cisplatin-etoposide was considered essential for a chance of cure. In order to administer the full cisplatin dose, 4-hour hemodialysis sessions were performed after each cisplatin infusion. During treatment cycle 3, 4 and 5, total and unbound plasma platinum concentrations were measured. Trough concentrations and half-life were at the higher end of the range of those observed in patients with adequate renal function who received the same dose of cisplatin. Hemodialysis aided platinum clearance, although our patient was also able to clear some platinum by his own renal function. With this full dose treatment, our patient obtained a favorable tumor response, with a strong decrease of beta-human chorionic gonadotropin and tumor size. The side effects experienced by our patient were serious, although not worse than what could be expected with this type of treatment. His renal function remained stable during the treatment period