Das Nierenzellkarzinom beim Kind

Renal cell carcinoma (RCC) is a very rare pediatric disease and should be treated as an entity of its own because of differences in symptoms, therapy, and prognosis from the adult form of the disease. Our objective is to discuss the difficulties in clinical diagnosis, prognosis, and therapy of this very rare disease in children and to provide a review of the current literature.     

Liver resection-associated macrophage inflammatory protein-2 stimulates engraftment but not growth of colorectal metastasis at extrahepatic sites

BACKGROUND: Previous studies have shown that liver resection enhances intrahepatic engraftment of CXCR-2-expressing colorectal cancer cells by the action of the CXC chemokine macrophage inflammatory protein (MIP)-2. Herein we studied how liver resection-associated MIP-2 affects extrahepatic tumor cell engraftment and whether MIP-2 also stimulates the growth of already established metastases. MATERIALS AND METHODS: Green fluorescent protein-transfected CT26.WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Additionally, all animals underwent a 30% hepatectomy. To study MIP-2 in extrahepatic tumor cell engraftment, animals were treated with an anti-MIP-2 antibody, starting at the day of tumor cell implantation. To study MIP-2 in established metastases, anti-MIP-2 treatment was initiated at day 5 after tumor cell implantation. Hepatectomized animals without neutralization of MIP-2 served as controls. Tumor vascularization and growth as well as tumor cell migration, proliferation, apoptosis, and CXCR-2 expression were studied over 14 days using intravital fluorescence microscopy, histology, and immunohistochemistry. RESULTS: Functional inhibition of MIP-2 significantly delayed extrahepatic tumor cell engraftment but not the growth of established metastases. The initial delay of engraftment was associated with a compensatory stimulation of vascularization and tumor cell migration when compared to controls (P < 0.05). Further, inhibition of tumor cell engraftment by initial anti-MIP-2 treatment was associated with a significant (P < 0.05) reduction of CXCR-2 expression and tumor cell apoptosis. CONCLUSION: Our study indicates that MIP-2 is involved in extrahepatic engraftment of CT.26 colorectal cancer cells. The MIP-2/CXCR-2 signaling pathway may be a promising target for early antitumor therapy in patients undergoing liver resection.     

Signet-ring cell formation in cutaneous neoplasms.

BACKGROUND: Signet-ring cells are formed by intracytoplasmic accumulations of various substances that push the nucleus to the cellular border. Signet-ring cells in epithelial neoplasms are often regarded as evidence of adenocarcinoma. OBJECTIVE: The study surveys the rare settings in which signet-ring cells are encountered in dermatopathologic specimens and investigates mechanisms of their formation. METHODS: A total of 23 cutaneous tumors with a significant population of signet-ring cells were studied by immunohistochemistry and electron microscopy. RESULTS: Signet-ring cells were found in a variety of cutaneous neoplasms, including primary cutaneous squamous and basal cell carcinoma and melanoma, as well as in metastatic adenocarcinoma. In all but the metastatic adenocarcinomas the vacuoles were periodic acid Schiff (PAS), PAS-digest, and colloidal iron negative. There was no staining of the vacuoles with antibodies against keratins and vimentin. Electron microscopy showed only empty spaces in all cases. CONCLUSION: The signet-ring like appearance of the cells in most of these conditions is probably the result of coalescence of intracytoplasmic vacuoles and not accumulation of secretory products. Signet-ring formation is not specific for cellular lineage but can occur in a variety of cutaneous neoplasms, analogous to other cellular alterations as rhabdoid, granular, clear, spindle, and balloon cells and oncocytes.     

Pharmakotherapie und intensivmedizinische Aspekte des Status epilepticus: Update 2020/2021

Die Anaesthesiologie - Die gezielte Therapie epileptischer Ereignisse und im Speziellen des Status epilepticus (SE) setzt das sichere Erkennen der Krankheitsbilder voraus, wofür gerade bei...     

Ventricular arrhythmia and torsade de pointe: Dose limiting toxicities of the MDR-modulator S9788 in a phase I trial

Background: S9788 is a triazineaminopiperidine derivative capable of reversing multidrug resistance (MDR) in vitro. In preclinical models S9788 was several fold more potent MDR inhibitor than verapamil or cyclosporine. At P-glycoprotein (Pgp) blocking concentrations, S9788 appeared to have only very little toxicity.Patients and methods: In a two step phase I trial we treated 39 patients with refractory cancer with S9788 and bolus doxorubicin. The steps differed mainly in the S9788 infusion duration; in the first part 23 patients received the MDR-reversing drug S9788 over 30 minutes, in the second step of the study 16 patients were administered S9788 over 150 minutes. The doses of S9788 were escalated in cohorts of three patients up to a dose level (DL) of 96 mg/m2 on the 30 minutes infusion, and to 144 mg/m2 on the 150 minutes infusion. The pharmacokinetics of S9788 were determined.Results: With the 30-minute infusion schedule symptomatic cardiac arrhythmia were found to be dose limiting. In all patients at the highest DL transient cardiac repolarization prolongation with a long QT-interval on ECG was demonstrated. With the 150-minute administration schedule, S9788 could be escalated up to 144 mg/m2 without subjective toxicity. However, transient QT prolongation was present in all patients. A third degree AV-block and a QT increase of about 40% occurred at the highest DL. Asymptomatic torsade de pointe (DL 96 mg/m2) was demonstrated on Holter recording in one patient. Theses repolarization disturbances with QT increase were considered dose limiting toxicity and the trial was closed. No arrhythmia related death was noted. Pharmacokinetics were similar with both infusion schedules with a mean alpha half life of 11.3 and 13.2 minutes, for the 30-minute and 150-minute infusion, and a terminal half life of 13.5 and 15 hours, respectively. QTc prolongation duration appeared to be dose-dependent.Conclusions: With the tested infusion schedules, cardiac toxicity, in particular AV-blocks and QT prolongation, leading to ventricular arrhythmia and torsade de pointe, are the dose limiting toxicities of S9788. Our experience together with the observation of asymptomatic torsade de pointe in two other phase I trials of S9788 infused over six hours precluded the further clinical development of S9788.