A Retrospective Analysis of the Impact of Metastasectomy on Prognostic Survival According to Metastatic Organs in Patients With Metastatic Renal Cell Carcinoma

This study evaluated the effects of metastasectomy on overall survival (OS) and progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC) according to metastatic organs. The medical records (2005–2017) of 273 patients with mRCC were analyzed retrospectively to evaluate OS and PFS according to metastatic organs and their metastasectomy states. The Cox proportional hazard model was used to determine the prognostic significance of metastasectomy. The Kaplan-Meier curve and log-rank test were used to compare groups with different modalities and metastatic organs at a statistical significance of p < 0.05. The overall median age was 57 years; 175 (64.3%) and 83 (30.4%) patients received cytoreductive nephrectomy and metastasectomy, respectively. The metastasectomy group was significantly younger and had a lower clinical T stage with significantly better PFS/OS (20.2/32.0 vs. 9.7/12.8 months) than that in the non-metastasectomy group (N = 190, p < 0.05). Liver with lung metastases were the worst metastatic combination for survivals in which liver metastasis was the only significant unfavorable risk factor for both PFS (HR 1.67) and OS (HR 1.74) (p < 0.05). Multivariable analysis confirmed that metastasectomy was a significant favorable risk factor for PFS (HR 0.70) and OS (HR 0.56) (p < 0.05) along with non-clear cell type (HR 0.61 for PFS), whereas the nuclear grade and poor Heng risk group were unfavorable risk factors (HR > 2.0) for both PFS and OS (p < 0.05). Metastasectomy and the affected metastatic organs significantly influenced prognostic survival in mRCC

Prostate Specific Membrane Antigen mRNA in Blood as a Potential Predictor of Biochemical Recurrence after Radical Prostatectomy

We investigated whether the detection of prostate specific membrane antigen (PSMA) in blood preoperatively has predictive value for biochemical recurrence (BCR) after radical prostatectomy in patients with prostate cancer. All 134 patients scheduled to receive radical prostatectomy for prostate cancer were prospectively enrolled. The authors used nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect PSMA mRNA-bearing cells in peripheral blood, and analyzed the ability of PSMA mRNA positivity to predict BCR after surgery. PSMA-mRNA was detected in 24 (17.9%) patients by RT-PCR. Over a median follow-up of 20 months (range, 3 to 46 months), BCR developed in 15 patients (11.2%) and median time to BCR was 7 months (range, 3 to 25 months). Kaplan-Meier analysis revealed a significant difference between those positive or negative for PSMA in terms of recurrence-free actuarial probability (log rank P=0.0039). Multivariate analysis showed that positivity for PSMA mRNA (HR: 3.697, 95% CI 1.285-10.634, P=0.015) and a biopsy Gleason score of ≥7 (HR: 4.500, 95% CI 1.419-14.274, P=0.011) were independent preoperative predictors of BCR. The presence of PSMA mRNA in peripheral blood can be used to predict BCR after radical prostatectomy

Analysis of Changes in the Total Lymphocyte and Eosinophil Count during Immunotherapy for Metastatic Renal Cell Carcinoma: Correlation with Response and Survival

The aims of this study were to analyze lymphocyte and eosinophil counts in consecutive peripheral blood samples taken during immunotherapy for metastatic renal cell carcinoma (mRCC) and to correlate the findings with objective response and survival. A total of 40 patients with mRCC who received immunotherapy with interleukin-2, interferon-α, and 5-fluorouracil were analyzed. Objective responses were observed in 14 patients, including 2 (5%) who showed a complete response (CR) and 12 (30%) who showed a partial response (PR). Eleven patients (27%) achieved stable disease (SD), and 15 patients (38%) had progressive disease (PD). Changes from baseline in the total lymphocyte counts were significantly higher in the responding patients (CR+PR+SD) than in the non-responding patients (PD) (p=0.017), but no difference was seen in the total eosinophil counts (p=0.275). Univariate analysis identified the Eastern Cooperative Oncology Group (ECOG) performance status (p=0.017), the presence of a primary renal tumor (p<0.001) and the peripheral lymphocyte counts at week 4 (p=0.034) as prognostic factors, but a low ECOG performance status (p=0.003) and the presence of a primary renal tumor (p=0.001) were identified as independent poor prognostic factors by multivariate analysis. This study provides further evidence that changes in blood lymphocyte counts may serve as an objective indicator of objective responses

Current Status of Targeted Therapy for Advanced Renal Cell Carcinoma

The treatment of metastatic renal cell carcinoma (mRCC) has recently evolved from being predominantly cytokine-based treatment to the use of targeted agents, which include sorafenib, sunitinib, bevacizumab (plus interferon alpha [IFN-α]), temsirolimus, everolimus, pazopanib, and most recently, axitinib. Improved understanding of the molecular pathways implicated in the pathogenesis of RCC has led to the development of specific targeted therapies for treating the disease. In Korea, it has been 5 years since targeted therapy became available for mRCC. Thus, we now have broader and better therapeutic options at hand, leading to a significantly improved prognosis for patients with mRCC. However, the treatment of mRCC remains a challenge and a major health problem. Many questions remain on the efficacy of combination treatments and on the best methods for achieving complete remission. Additional studies are needed to optimize the use of these agents by identifying those patients who would most benefit and by elucidating the best means of delivering these agents, either in combination or as sequential single agents. Furthermore, numerous ongoing research activities aim at improving the benefits of the new compounds in the metastatic situation or their application in the early phase of the disease. This review introduces what is currently known regarding the fundamental biology that underlies clear cell RCC, summarizes the clinical evidence supporting the benefits of targeted agents in mRCC treatment, discusses survival endpoints used in pivotal clinical trials, and outlines future research directions

Gamma frequency entrainment attenuates amyloid load and modifies microglia

Changes in gamma oscillations (20-50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer's disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-β (Aβ)[subscript 1-40] and Aβ [subscript 1-42] isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with Aβ. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced Aβ[subscript 1-40] and Aβ[subscript 1-42] levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.National Institutes of Health (U.S.) (Grant 1R01EY023173)National Institutes of Health (U.S.) (Grant 1DP1NS087724)National Institutes of Health (U.S.) (Grant RF1AG047661)National Institutes of Health (U.S.) (Grant ROIGM104948

SETD2, GIGYF2, FGFR3, BCR, KMT2C, and TSC2 as candidate genes for differentiating multilocular cystic renal neoplasm of low malignant potential from clear cell renal cell carcinoma with cystic change

Purpose: Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and clear cell renal cell carcinoma with cystic change (MCRCC) have different prognoses despite similar histologic characteristics. The aim of this study was to identify differentially mutated genes in resected tumor specimens from patients diagnosed with MCRNLMP and MCRCC using a kidney cancer gene panel. Materials and Methods: Between 2009 and 2016, 13 MCRNLMP and 17 MCRCC cases were selected. Tumor tissues from 5 MCRNLMP and 16 MCRCC cases were subjected to gene sequencing to detect mutations among 88 genes selected from a kidney cancer gene panel after quality control. Fisher's exact test was used to compare gene mutation profiles between the two diseases. Genes were considered to be positive for mutation according to the presence of an in-frame/frameshift deletion or insertion, missense/nonsense mutation, or multi-hit mutation. Results: During a median follow-up period of 66.2 months, there was only one case of MCRCC recurrence among all 30 patients. Target gene sequencing showed that 35 genes tended to be more frequently positive in either disease group, with six genes showing a significantly different frequency of mutation between the groups: GIGYF2 (odds ratio [OR], 5.735), FGFR3 (OR, 6.787), SETD2 (OR, 4.588), BCR (OR, 6.266), KMT2C (OR, 8.167), and TSC2 (OR, 4.474). Conclusions: Six candidate genes showed significantly different mutation patterns between MCRNLMP and MCRCC, providing insight into their pathogenic mechanisms and differential prognoses