Retrospective multicentre study of carboplatin monotherapy for clinical stage I seminoma.

OBJECTIVE: • To evaluate, in a retrospective multicentre study, the long-term oncological efficacy and morbidity of using carboplatin as an alternative treatment for patients with clinical stage I seminoma. PATIENTS AND METHODS: • Patients with clinical stage I seminoma treated with two cycles of adjuvant single-agent carboplatin (400 mg/m² body surface) from February 1990 until September 2008 were retrospectively identified. • A database was created (including information on patient characteristics, initial tumour staging, tumour marker levels, follow-up, oncological outcome, treatment side effects and long-term side effects), descriptive analyses were performed and the data were compared with those available in the literature. RESULTS: • Of 282 stage I seminomas identified in 276 patients, risk factors for progression (pT2/3, vessel invasion or tumour diameter ≥ 4 cm) were detected in 48.2% of tumours. • Chemotherapy was well tolerated, with patients experiencing only mild nausea. Bone marrow suppression was common (leucopaenia in 36.7% and thrombocytopaenia in 50.5% of patients, mainly grade 1/2). Neither neutropenic fever, nor any bleeding complication occurred. • During a mean follow-up of 75 months, three patients (1.06%) developed a retroperitoneal recurrence within the first 2 years after receiving adjuvant treatment and were salvaged by cisplatin-based chemotherapy. A contralateral second testicular germ cell tumour was diagnosed in five patients. CONCLUSIONS: • Two cycles of carboplatin monotherapy are highly effective and very well tolerated by all patients. The frequency of contralateral tumours appears to be reduced. • Despite the lack of a randomized trial, the available data in the literature suggest that the administration of two cycles instead of one cycle could lead to a reduction in recurrence rates of ≈50%.

Immunohistochemical localization of apolipoprotein A-IV in human kidney tissue.

BACKGROUND: Apolipoprotein A-IV (ApoA-IV) is a 46 kD glycoprotein thought to protect against atherosclerosis. It is synthesized primarily in epithelial cells of the small intestine. Elevated plasma concentrations of ApoA-IV in patients with chronic kidney disease suggest that the human kidney is involved in ApoA-IV metabolism. METHODS: To investigate whether the human kidney directly metabolizes ApoA-IV and which kidney tissue compartment is involved therein, ApoA-IV was localized by immunohistochemistry in 28 healthy kidney tissue samples obtained from patients undergoing nephrectomy. ApoA-IV mRNA expression was analyzed by real-time polymerase chain reaction (PCR) to exclude de novo synthesis in the kidney. RESULTS: ApoA-IV immunostaining was detected in proximal and distal tubular cells, capillaries and blood vessels but not inside glomeruli. ApoA-IV was predominantly found in the brush border of proximal tubules and in intracellular granules and various plasma membrane domains of both proximal and distal tubules. mRNA expression analysis revealed that no ApoA-IV was produced in the kidney. CONCLUSION: The immunoreactivity of ApoA-IV observed in kidney tubular cells suggests a direct role of the human kidney in ApoA-IV metabolism. The granular staining pattern probably represents lysosomes degrading ApoA-IV. The additional ApoA-IV localization in distal tubules suggests a rescue function to reabsorb otherwise escaping ApoA-IV in case proximal tubules cannot reabsorb all ApoA-IV. Since no mRNA expression could be detected in any kidney cells, the observed ApoA-IV immunoreactivity represents uptake and not de novo synthesis of ApoA-IV.