Does Additional Doxorubicin Chemotherapy Improve Outcome in Patients with Hepatocellular Carcinoma Treated by Liver Transplantation?

The aim of this prospective randomized study was to determine whether additional doxorubicin chemotherapy improves outcome in patients with hepatocellular carcinoma (HCCA) treated by liver transplantation. Stratification parameters were tumor stage (UICC I-IVa), gender, age 50 years, α-fetoprotein 20 ng/mL, cirrhosis and HbsAg status. For pre-operative chemotherapy doxorubicin (15 mg/m²) was given biweekly, intra-operative chemotherapy was a single dose administered before surgical manipulation. Post-operative chemotherapy from day 10 was as given preoperatively for a total dosage of 300 mg/m². Outcome parameters were overall survival (OS) and disease-free survival. Of the 75 consecutive patients who received liver transplantation for treatment of HCCA, 62 patients were enrolled. Thirty-four patients were randomized in the chemotherapy group; 28 patients were in the control group and transplanted only. OS rates at 5 years were 38% in the chemotherapy group and 40% in the control group, disease-free survival rates at 5 years 43% and 53%, respectively. Tumor stage and vascular invasion were identified as independent risk factors for recurrence of disease. Doxorubicin chemotherapy did not improve organ survival and disease-free survival in patients undergoing liver transplantation for HCCA.     

Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro

Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen     

A large mediastinal tumour?

A 72-year-old man with increasing shortness of breath and atypicalangina pectoris received a chest radiograph     

Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle

Human Molecular Genetics     

Safety of thrombolysis during cardiopulmonary resuscitation.

The prognosis is generally poor for patients who experience a cardiac arrest. The most common causes of sudden cardiac arrest are massive pulmonary embolism (PE) and acute myocardial infarction (MI). While thrombolysis is a first-line treatment option in massive PE and acute MI, cardiopulmonary resuscitation (CPR) has been regarded as a relative contraindication for thrombolysis because of the anticipated bleeding risk caused by traumatic cardiocompressions. However, an increasing number of case reports and clinical studies on thrombolysis during and after CPR highlight an increased frequency of the return of spontaneous circulation and a better neurological outcome of surviving patients. These effects are mainly due to the thrombolysis of macroscopic blood clots and the amelioration of microcirculatory reperfusion.This article reviews case reports and clinical studies of thrombolysis during and shortly after CPR in order to estimate the risk of severe bleeding events caused by CPR in association with thrombolysis compared with CPR without thrombolysis.Although thrombolysis per se can cause severe and potentially fatal haemorrhage, there is no evidence that severe bleeding events occur more often when thrombolysis is combined with cardiocompressions. In addition, by far the majority of bleeding complications can be treated effectively. Thus, in many cases, the possible benefit of thrombolysis during CPR seems to outweigh the potential risks. However, there may be a publication bias in some case reports and studies towards reporting successful rather than unsuccessful CPRs. In addition, not enough controlled clinical trials have yet been conducted. Therefore, data from large randomised, multicentre studies are needed to definitely answer the question of the relationship between safety and efficacy of this promising treatment option.We conclude that the currently available data do not indicate that thrombolysis contributes to a significant increase in bleeding complications when administered during CPR.