Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.

A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.     

HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P<0.02) and 5 years (36% vs. 72%, P<0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P<0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses. Received September 19, 1995; received in revised form and accepted April 16, 1996     

Urination Frequency and Cystic Pressure Resistance After Fractionated whole or Partial Irradiation of the Rabbit Urinary Bladder

Urination frequency and cystic pressure resistance have been used as end-points to assess x-ray-induced changes of bladder function. Whole or half bladders of adult male rabbits were irradiated, caudally or cranially. The absorbed dose was 33 Gy, 36 Gy or 39 Gy, given in 5 daily fractions. Animals which received a whole bladder dose of 39 Gy or 36 Gy showed increased urination frequency and enhanced bladder pressure resistance during the whole follow-up time of 100 weeks, compared with the sham-irradiated controls. At half bladder irradiation, only the highest doses (39 Gy to the cranial part of the bladder and 39 Gy or 36 Gy to the caudal part) gave rise to a slight increase in frequency at about 20 weeks after exposure.     

Cisplatinum Dose Dependent Response in Germ Cell Cancer Evaluated by Tumour Marker Modelling

This study presents an analysis on longitudinal tumour marker series in twenty-two patients with non-seminomatous germ cell cancers treated with cisplatinum (DDP) based combination chemotherapy. Series of alphafoetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) were analyzed applying a dynamic mathematical marker model. The model analysis provided quantitated values for growth rate and treatment response in the marker producing cells. The analysis showed that LDH had to be above 2 000 U/l to be a trustworthy tumour marker. HCG producing cells tended to grow faster than AFP producing cells, and were 3-5-fold more sensitive to the chemotherapy given than AFP producing cells. Treatment response versus DDP dose appeared to be bi-phasic, but with no significant change in treatment efficiency within the given range of DDP doses.     

Radiological detection of bone and bone marrow metastases

Bone scintigraphy is the primary method for the diagnosis of skeletal métastases. This investigation is sensitive, but the interpretation must be performed in the knowledge that it is also nonspecific. Despite this, a correct diagnosis can usually be achieved. The first-hand supplementary investigation, after a doubtful scintigraphic finding, is radiography. In most cases this is sufficient for a diagnosis. When a scintigraphic abnormality cannot be adequately explained, usually because of a negative radiographic examination, a more sensitive modality must be used. Computerized tomography offers increased sensitivity and specificity, and is primarily used for this purpose. In this way contrast resolution is increased and problems caused by obscuring tissue and complicated anatomy are reduced. Since bone metastases migrate via the active bone marrow an alternative supplementary investigation is bone marrow scintigraphy. Its usefulness is restricted by disturbing activity, from the liver and the spleen, which obscures a significant part of the active marrow, and by the fact that a lesion must be of a certain size to become apparent. Magnetic resonance imaging yields excellent images of the extension of a tumor in soft tissue. Owing to high costs and restricted availability it is still mainly used for preoperative location of metastases.     

Case report: fusion of positron emission tomography (PET) and computed tomography (CT) images for image-guided endoscopic navigation in maxillofacial surgery: clinical application of a new technique.

INTRODUCTION: Surgery based on computed tomography (CT) data is becoming increasingly important in the head and neck region. The technique for hardware fusion between positron emission tomography (PET) and computed tomography (CT) has only been established commercially in the last 4 years. The advantages over CT alone are obvious. The surgeon is simultaneously provided with a map of anatomical as well as of functional (metabolic) details. The fused images offer improved localization of malignant lesions and improved targeting of biopsy, especially for small lesions. PURPOSE: A new technique for image-guided tumour localization for maxillofacial surgery based on PET/CT-image fusion is described. PATIENT AND METHOD: A 78-year-old woman was admitted to this department with a tumour of the skull base. Three dimensional fusion of computed CT with positron PET images on a commercially available navigation system is described. After patient-to-image registration, a high-resolution endoscope was calibrated intraoperatively. Image-guided biopsy specimens were taken under direct visual control. CONCLUSION: PET/CT-image fusion proved extremely helpful to navigate the endoscope to the target lesion and to identify the tumour.     

Evidence for a human IgG1 class switch program

In activated murine B lymphocytes, immunoglobulin class switch recombination occurs as a highly regulated process which is targeted to distinct switch regions. Here we present first evidence that in human B lymphocytes, switch recombination is targeted to distinct switch regions as well. In a panel of clonally unrelated IgG1-expressing human B cells, immortalized by Epstein-Barr virus (EBV) transformation, seven out of nine cells show switch recombination between Sμ and Sγ1 on both alleles, the active and inactive one. The remaining cells show no switch recombination on the inactive IgH locus. The very strong correlation of switch recombination on both alleles of IgG1-expressing cells proves that class switch recombination to IgG1 is not random but directed in human B lymphocytes.