Temsirolimus for advanced renal cell carcinoma.

Renal cell carcinomas (RCCs) represent one of the ten leading cancer entities with an increasing incidence especially in the western world. Unfortunately, about 25% of the patients develop metastatic RCC (mRCC) associated with a most unfavorable prognosis. In the recent years, various new agents targeting VEGF or VEGF receptor (VEGFR) or the mTOR pathway have been approved for the treatment of mRCC with significant prolongation of progression-free survival and, in part, of overall survival (OS). Targeting the mTOR kinase is an interesting option for mRCC. Temsirolimus, one of the available mTOR inhibitors, has been approved as a single agent in poor-risk mRCC patients based on the pivotal Phase III trial showing a significant superiority in OS versus IFN-α or temsirolimus + IFN-α, which has been verified by a pivotal Phase III trial. The benefit has been shown for clear cell carcinoma and papillary RCC as well. For poor prognosis patients, temsirolimus improves median survival by 3.6 months. In second-line treatment compared with sorafenib following first-line treatment with sunitinib temsirolimus showed a relative progression-free survival benefit for patients with nonclear cell RCC with temsirolimus. The median OS for the temsirolimus group was 12.27 and 16.64 months for the sorafenib group. In 2007, the US FDA granted approval for temsirolimus for the treatment of advanced RCC.

[Periprocedual management of vitamin K antagonist's with low molecular weight heparins during invasive procedures--Consensus of experts]. / Niedermolekulare Heparine zur Überbrückung der Pause von Vitamin-K-Antagonisten während interventioneller Eingriffe ­ Expertenkonsensus.

Interruption of an ongoing therapy with vitamin K antagonists (VKAs) is necessary in almost all patients undergoing major surgery. The purpose of the following expert recommendations is to provide easy to use guidance for the periprocedural management of patients on VKAs based on current evidence from the literature. Management of anticoagulation during the time of interruption of VKAs is based on balancing the thromboembolic (TE) risk of underlying conditions against the bleeding risk of the surgical procedure. VKAs should be stopped 3­7days prior to surgery. Low molecular weight heparin (LMWH) is used to cover ("bridge") the progressive pre-operative loss of anticoagulation and the slow post-operative onset of anticoagulant activity of VKAs. Patients with high risk of TE should receive a therapeutic dose of LMWH, patients with a moderate risk of TE should receive half of this dose. Patients with a low risk of TE do not need bridging therapy with LMWH. In case of an uneventful postoperative course, patients with a therapeutic pre-operative dose should be treated post-operatively with the same dose, starting on day 4 in case of major surgery and on day 2 in case of minor procedures. Patients with a half-therapeutic preoperative dose should be treated post-operatively with the same dose, starting on day 3 in case of major surgery and on day 1 in case of minor procedures. Therapy with VKAs should be re-instituted on the second post-operative day based on the preoperative dosage. Procedure-related post-operative thromboprophylaxis should be given irrespective of these recommendations on days without "bridging" anticoagulation.

Chorioangioma--new insights into a well-known problem. I. Results of a clinical and morphological study of 136 cases.

AIMS: Chorioangiomas are rare hamartomatous lesions. Possible correlations between their occurrence and the progression of a pregnancy have been objects of discussions for quite some time. METHODS: In a retrospective study 22439 unselected placentas were examined for incidences of chorioangiomas, morphological features and accompanying clinical characteristics. RESULTS: Chorioangiomas occur in 0.61% of pregnancies, they are mainly microscopically small, and 55% of them are localized subchorial. The rate of their occurrence rises almost linearly with maternal age; chorioangiomas are found most often in women who are over 30 years old. Hypertension and diabetes are found more often in combination with chorioangiomas than they are in otherwise normal pregnancies. In 72% of all cases girls were born; in 33% we also observed malfunctions in the maturation processes of the placental parenchyma, in particular arrested and delayed maturation of the villi. Premature births occur approximately three times more often in chorioangioma pregnancies than in normal ones. Chorioangiomas are often found in primipara and twin pregnancies.

Chorioangiomas--new insights into a well-known problem. II. An immuno-histochemical investigation of 136 cases.

AIMS: Chorioangiomas are benign tumors of the hemochorial placenta. They are malformations or hamartomas, formed as a result of defective angiogenesis. They are of clinical importance due to their association with premature placental release and pre-eclampsia. METHODS: Since a link has been established in neoplasias between tumor growth and an increased expression of angiogenic growth factors, 136 samples of chorioangiomas and 136 samples of tumor-free placental tissue were examined in terms of proliferation rate and expression of the growth factors angiopoietin-1 and -2, the angiopoietin-receptor Tie-2, PDGF and the PDFG beta-receptor. RESULTS: The chorioangiomas exhibited differing proliferation rates, whereas tumor-free placental tissue barely proliferated at all. Angiopoietin expression was--morphologically--considerably higher within the chorioangiomas than in the comparison placentas; morphological amounts of the Tie-2 receptor were identical in all samples. Expression of PDGF and its receptor was the same for chorioangiomas and tumor-free placentas. CONCLUSIONS: According to this study and the current literature in the field of hamartomas and some neoplasia, we can assume that increased growth factor expression plays a role in the formation of chorioangiomas, since it stimulates proliferation in a wide variety of cell compartments.

Myoid differentiation in mesoblastic nephroma: clinicopathologic and cytogenetic findings of a rare case.

The authors report the case of a benign renal mesenchymal tumor in a baby boy detected by ultrasound scanning during prenatal diagnosis. Histologically, the tumor was diagnosed as a congenital mesoblastic nephroma (CMN) with myoid differentiation. The tumor normally is characterized by a fascicular proliferation of bland, spindle-shaped cells. CMN is the most common renal tumor in the neonatal period and presumedly results from a neoplastic transformation affecting the pluripotent mesodermal nephric blastema. In embryonic life, tumorigenic influences acting on the nephric blastema might result in selective overgrowth of its mesoblastic derivates. CMN must be differentiated from other spindle-shaped tumors, like Wilms' tumor, rhabdoid tumor of the kidney, clear cell sarcoma, nephrogenic adenofibroma, fibroma and fibrosarcoma, leiomyoma, metanephric stromal tumor, and, in this case especially, from tumors with myoid differentiation like infantile myofibromatosis. Numerical molecular abnormalities are observed frequently in renal mesenchymal tumors, especially in chromosome 11. Cytogenetic findings in our tumor after comparative genomic hybridization (CGH) showed full trisomies of chromosomes 20 and 22q, partial trisomies for the distal part of 11q and 1p, and an approximately full monosomy of chromosome 4 (4qter-4p15). The chromosomal imbalances of the tumor can be described as: rev ish enh(1p31pter,11q23qter,20,22), dim(4)(p15qter).