Masayuki Yuzawa

Effects of Dosing Time and Schedule on Cisplatin‐Induced Nephrotoxicity in Rats

Renal dysfunction induced by a single injection of cisplatin depends on the timing of the dose. However, the effects of repeated administration of cisplatin on time‐dependent toxicity have not been evaluated despite the fact that in clinical practice high doses are repeatedly injected at intervals or low doses are administered daily. We studied chrono‐nephrotoxicity in rats after weekly or daily cisplatin injections.

Effect of citrate and pyrophosphate on the stability of calcium oxalate dihydrate

Abstract The effect of citrate and pyrophosphate on the stability of calcium oxalate dihydrate (COD) was studied in an aqueous solution over 7 days. COD was precipitated from 1.0 × 10−2 mol/l calcium oxalate solution with the addition of citrate and/or pyrophosphate and separated by centrifugation immediately, 48 h and 7␣days after the precipitation. The percentage of COD in the precipitate, determined by X-ray diffraction, increased with a rise in citrate or pyrophosphate concentration and reached ≥90% at a citrate concentration of 1.0 × 10−3 mol/l or a pyrophosphate concentration of 2.0 × 10−4 mol/l. The resulting COD was completely transformed into calcium oxalate monohydrate within 48 h when the precipitate was composed of <90% COD. Nearly pure COD produced with pyrophosphate was stable over 7 days while that with citrate underwent partial transformation within 48 h. An additive effect of citrate and pyrophosphate was found on the stability of COD. It was concluded that a pyrophosphate concentration above a critical point was sufficient to prevent solution-mediated transformation of COD, and this critical point might be lowered to the physiological range with the presence of citrate.

Clinical outcome and prognostic survival factors in patients with advanced renal cell carcinoma treated with very low-dose interleukin-2, interferon-α, and tegafur-uracil: a single-institution experience

BackgroundThe objective of the current study was to determine the efficacy and safety of very low-dose interleukin-2 (IL-2), interferon (IFN)-α, and tegafur-uracil for patients with unresectable renal cell carcinoma (RCC), metastatic RCC, or both. Clinical prognostic factors were also investigated.MethodsFifty consecutive patients underwent a 3-week treatment cycle of IL-2 (0.7 × 106 Japanese reference units [JRU])/person on days 1–3 weekly), IFN-α (3 × 106 international units/person, on days 1–5 weekly), and tegafururacil (300 mg/person daily).ResultsThe median follow-up after treatment initiation was 11.3 months. A median of three (range, 1–20) treatment cycles was administered. Of 47 eligible patients, 4 had a treatment response (3 complete responses and 1 partial response; objective response rate, 8.5%). The median progression-free and overall survivals were 8.3 months (95% confidence interval [CI], 5.5–10.9 months) and 38.8 months (95% CI, 27.8–49.7 months), respectively. Only 8 patients had grade III/IV toxicities. Two parameters, i.e., the absence of a previous nephrectomy and a low hemoglobin level, were identified as independent factors predictive of poor survival. Patients with low or intermediate risk (presence of none or one of the two prognostic factors) had a durable median survival exceeding 30 months. High-risk patients with both risk factors had rapid disease progression despite treatment.ConclusionWhile the effectiveness of this immunochemotherapy resulted in a limited antitumor response, low-and intermediate-risk patients with metastatic RCC seemed likely to have a survival benefit. Patient selection is essential to enhance treatment efficiency and avoid useless treatment for high-risk patients.

Rare renal pseudotumor associated with chronic glomerulonephritis mimicking renal cell carcinoma.

We describe a unique case of chronic glomerulonephritis that simulated a renal neoplasm observed on abnormal imaging. Histologic examination of the resected specimen supported the assumption that the observed mass lesion resulted from regional sparing in the development of chronic glomerulonephritis. We believe this case is the first to show the etiology of pseudotumor as an extremely uncommon manifestation of chronic glomerulonephritis by histologic examination.

Different responses to two types of 5-fluorouracil prodrugs in combination with interferon-alpha in pulmonary metastases of renal cell carcinoma: a case report

A 66-year-old Japanese man with pulmonary metastases of renal cell carcinoma found 8 months after radical nephrectomy was treated with interferon-alpha and tegafur-uracil. Since it failed to achieve tumor responses resulting in progression, he was given interferon-alpha and capecitabine. After 2 courses of combination therapy with IFN-alpha and capecitabine, significant tumor responses were obtained; two out of four pulmonary metastatic sites disappeared completely, one site showed over 50% decrease in size, and the remaining one site did no change in size. The regimen was well tolerated and toxicity observed was World Health Organization grade 1 anorexia. His disease status was maintained as stable disease by the repeated treatment with interferon-alpha and capecitabine for 17 months after tumor responses were obtained. However, tumor progression was observed thereafter. He is at present under treatment with sorafenib. This is the first case report of metastatic renal cell carcinoma, which showed different responses to two types of 5-fluorouracil prodrugs in combination with interferon-alpha, suggesting the biochemical modulation of capecitabine by interferon-alpha as a possible mechanism underlying the antitumor effect of the combination of interferon-alpha and capecitabine at the clinical setting. Present case also suggests that a combination of tumor-selective capecitabine with interferon-alpha is a potentially useful therapeutic option in metastatic renal cell carcinoma.