Pathologic complete response with pembrolizumab plus axitinib in metastatic renal cell carcinoma.

Immunotherapy-based combinations have played a central role in the treatment of metastatic renal cell carcinoma, and long-term survival of patients is expected. In this context, it is clear that a certain number of patients can achieve a complete response. However, the diagnosis of complete response is usually based on imaging, and there are few cases of pathological complete response. In this study, we report a case of a patient with metastatic renal cell carcinoma who was treated with pembrolizumab plus axitinib, followed by resection of the primary tumor and metastatic lesions, and pathologically achieved a complete response.

Time to progression to castration-resistant prostate cancer after commencing combined androgen blockade for advanced hormone-sensitive prostate cancer.

PURPOSE: The aim of our retrospective study was to determine the time to progression to castration-resistant prostate cancer (CRPC) in prostate cancer patients who undergo combined androgen blockade (CAB), as well as their prognoses. MATERIALS AND METHODS: We examined the overall survival (OS) and disease-specific survival rates, as well as the time to CRPC development, in 387 patients who were treated with CAB for prostate cancer. The disease-specific survival rate and time to CRPC were stratified by prostate-specific antigen (PSA) levels, Gleason score (GS), and presence of metastasis at diagnosis. We designated high-risk patients as those satisfying at least two of the following three criteria: extent of disease of bone metastasis grade ≥2, presence of metastasis at diagnosis, and a GS ≥8. RESULTS: The 10- and 15-year OS rates were 74.0% and 50.4%, respectively, while the corresponding disease-specific survival rates were both 86.8%. Metastasis at diagnosis was an independent prognostic factor for disease-specific survival. The median time to CRPC development was 140.7 months. A PSA level ≥20 ng/mL, a GS ≥8, and the presence of metastasis at diagnosis were independent predictors of a shorter time to CRPC development. The 10-year disease-specific survival rate in the high-risk group was significantly lower than that in the low-risk group (approximately 74% vs. 98%), and the time to CRPC development was significantly shorter (median: 20.5 months vs. not reached). CONCLUSIONS: The time to CRPC development was shorter in high-risk prostate cancer patients with metastases. Such patients require alternative novel treatment modalities.

A study of innate immunity in patients with end-stage renal disease: special reference to toll-like receptor-2 and -4 expression in peripheral blood monocytes of hemodialysis patients.

It was recently shown that toll-like receptors (TLR) play a critical role in innate immunity. However, no study has been conducted on TLR expression in hemodialysis (HD) patients. The present study was undertaken to examine innate immunity and the roles played by endotoxins (ET) contained in dialysate in HD patients, by analysis of TLR expression and reactivity. TLR-2 and TLR-4 expression on monocytes was investigated by flow cytometry in the following groups of subjects: healthy controls, patients on HD, patients with end-stage renal disease (ESRD) and patients on peritoneal dialysis (PD). The expression of TLRs on monocytes under stimulation with lipopolysaccharide was also investigated. Expression of TLR-4 was lower in the HD group than in the healthy controls (p<0.05), while expression of TLR-2 was lower in the PD group than in the healthy controls (p<0.05). As the duration of dialysis became longer, TLR-4 expression decreased (p<0.01). TLR-2 was not correlated with duration of dialysis, and the magnitude of decrease in TLR-4 expression following stimulation with ET became smaller (p=0.0006). Suppression of expression of TLR-4 was noted in HD patients, and TLR-4 expression was reduced as the duration of dialysis became longer. Reduced TLR-4 expression may be associated with the compromised immune function in HD patients. It seems possible that chronic stimulation with ET suppresses the expression of TLR-4.

The effect of ultrapure dialysate on improving renal anemia.

BACKGROUND: Renal anemia is a very serious problem in hemodialysis patients. In this regard, the investigation was focused on whether ultrapure dialysate could improve renal anemia and the mechanism of renal anemia. METHODS: Ultrapure dialysate was used over a 2 years period for 61 patients on maintenance hemodialysis. During this period, the changes in renal anemia and red blood cell life span were investigated. The changes in the latter were evaluated using the creatine concentration in red blood cell. RESULTS: The hemoglobin concentration, RBC count, and hematocrit concentration before the use of the ultrapure dialysate were 9.1 +/- 0.2 g/dL, 309.9 +/- L7.2 x 10(4)/microL, and 28.8 +/- 0.6%, respectively. These values significantly increased to 10.2 +/- 0.1 g/dL, 349.7 +/- 5.6 x 10(4)/microL, and 32.6 +/- 0.3%, respectively, after 2 years of ultrapure dialysate use. The increase in reticulocyte count indicated enhanced erythropoiesis by ultrapure dialysate. The red blood cell life span evaluated by creatine concentration in red blood cell was also prolonged after the use of ultrapure dialysate. CONCLUSIONS: Ultrapure dialysate is considered to improve the renal anemia of dialysis patients by promoting erythropoiesis and prolonging red blood cell life span.