Enhancement of IL-2-induced cytotoxicity by interferon-alpha in renal cell carcinoma.

Metastatic renal cell carcinoma (mRCC) treatment consists of molecular targeted agents and cytokines that have fundamentally different mechanisms of action. Clinical responses also differ; complete response is rare with molecular targeted agents but is sometimes achieved with cytokine therapies. Because of the relatively high efficacy of combination therapy with low-dose interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) against mRCC, it is important to reevaluate cytokine therapies in vitro. Here, we show that when IL-2 is administered in combination with IFN-alpha, a stronger cytotoxic effect of PBMCs on RCC cell lines is observed than when IL-2 is administered alone. The upregulation of TNF-related apoptosis-inducing ligand on NK cell by IL-2 and suppression of regulatory T cells (Tregs) by IFN-alpha were recognized at the same time when cytotoxicity of peripheral blood mononuclear cells (PBMCs) was enhanced. IL-2 is known to activate natural killer cell cytotoxicity; however, IL-2 also stimulates Treg expansion, which enhances immunosuppression. On the other hand, IFN-alpha negatively regulates Treg cells, thereby increasing the function of immune effector cells. Our in vitro results may explain, at least in part, the clinical efficacy of combination low-dose IL-2 and IFN-alpha therapy against mRCC.

Impact of hospital volume on postoperative complications and in-hospital mortality after renal surgery: data from the Japanese Diagnosis Procedure Combination Database.

OBJECTIVES: Previous studies on the relationship between nephrectomy volume and outcomes focused mainly on operative mortality. Little is known about the association between operative volume and postoperative complications. This study analyzed the influence of hospital volume on postoperative complications and in-hospital mortality after nephrectomy or nephroureterectomy. METHODS: Using the Diagnosis Procedure Combination database in Japan, 7988 patients undergoing nephrectomy or nephroureterectomy between July and December in 2006 and 2007 were identified. The cases were divided into low (≤26/y), medium (27-64), or high (≥65) hospital volume groups. Logistic regression analyses were performed to model the concurrent effects of hospital volume and other factors on postoperative complications and in-hospital mortality. RESULTS: In-hospital mortality was 0.84%. The overall postoperative complication rate was 7.4%. Factors associated with mortality or morbidity were age, hypertension, chronic lung diseases, cardiac diseases, chronic renal failure, and duration of anesthesia. Video-assisted surgery showed a significantly lower rate of mortality (odds ratio [OR], 0.28; P <.01) and postoperative complications (OR, 0.47; P <.01) than open surgery. The difference of mortality between high and low-volume groups was not significant (0.5% vs 1.0%) (OR, 0.48; P = .089). Although higher hospital volume was associated with fewer postoperative complications (OR, 0.72; P = .014), the difference was slight (7.1% vs 7.8%). CONCLUSIONS: Less comorbidity and invasive surgery and shorter anesthesia were associated with lower mortality and morbidity after renal surgery. Despite volume disparities, the magnitude of difference was only 0.7% in complications and 0.5% in mortality.