Role of the Renin-Angiotensin System Components in Renal Cell Carcinoma: A Literature Review.

PURPOSE OF REVIEW: The physiological aspects of renin-angiotensin system (RAS) components are described in this review. Additionally, we present the main results of studies that could indicate an association between alterations in these components and cancer, particularly renal cell carcinoma (RCC). RECENT FINDINGS: The RAS undergoes a series of homeostatic and modulatory processes that extend to hypertrophy, hyperplasia, fibrosis, and remodeling, as well as angiogenesis, pro-inflammatory responses, cell differentiation, stem cell programming, and hematopoiesis. The link between cancer-related inflammation and RAS signaling converge in the response to tumor hypoxia and oxidative stress mechanisms, particularly with the angiotensin type 1 receptor leading to activation of transcription factors such as nuclear factor κB (NF-κB), as well as members of the signal transducer and activation of transcription (STAT) family and HIF1⍺. Dysregulation of the physiological actions of RAS in the microenvironment of inflammation and angiogenesis promotes tumor cell growth.

Primary laparoscopic RPLND for pure seminona metastasis: feasibility of supine and lateral approaches.

INTRODUCTION: Retroperitoneal lymphadenectomy (RPLND) is well established as a primary treatment, especially for high-risk stage I and stage IIA/B nonseminomatous tumors, but its value in seminomatous tumors is underreported (1). Classically, seminomas with isolated retroperitoneal lymphadenopathy are treated with external beam radiation therapy or systemic chemotherapy. Although these modalities are effective, they are associated with significant long-term morbidity (2, 3). Some retrospective studies have demonstrated the potential of RPLND as a first-line treatment for stage IIa seminoma, and two very recent prospective trials, still with interim results: SEMS TRIAL and PRIMETEST(3-7). The RPLND robotic technique has been previously described in the post-chemotherapy scenario, however, surgical videos of primary laparoscopic approach are lacking, especially in seminomatous disease (8). MATERIALS AND METHODS: We present two cases of primary videolaparoscopic RPLND, using different approaches. Case 1: Thirty four years-old, with prior right orchiectomy for mixed tumor. After 8 months he presented an two cm enlarged interaortocaval lymph node. Percutaneous biopsy showed pure seminoma metastasis. Case 2: Thirty three years-old, with previous left orchiectomy for stage I pure seminoma, without risk factors. After nine months, the patient had a three cm enlarged para-aortic lymph node. RESULTS: The surgical time ranged from 150 to 210 minutes, with a maximum bleeding of 300 mL and hospital discharge in 48 hours. In one of the cases, we identified a significant desmoplastic reaction, with firm adhesions to the great vessels, requiring vascular sutures, however, no major complication occurred. Pathological anatomy confirmed pure seminoma lymph node metastases in both cases. CONCLUSION: Laparoscopic primary RPLND proved to be technically feasible, with less postoperative pain and early hospital discharge. We understand that more studies should be performed to confirm our oncological results.

False-Positive Uptake in Splenic Hemangioma on 68Ga-PSMA PET/CT Scan for Late Biochemical Recurrence of Prostate Cancer.

ABSTRACT: A 71-year-old man underwent 68Ga-PSMA PET/CT for evaluation of a late biochemical recurrence after radical prostatectomy. An intense PSMA uptake was identified in spleen. Additional evaluation with a contrast-enhanced MRI showed a splenic lesion consistent with splenic hemangioma.

Prognostic Impact of Loss of SETD2 in Clear Cell Renal Cell Carcinoma.

PURPOSE: To evaluate the prognostic impact of immunohistochemical expression of SETD2 in patients with clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: A total of 662 patients with primary or metastatic ccRCC were evaluated. Two genitourinary pathologist reviewed all of the cases for uniform reclassification and determined the selection of the most representative tumor areas for construction of the tissue microarray (TMA). RESULTS: SETD2 nuclear staining showed that 101 areas (15.3%) had negative expression, and 561 areas (84,7%) had positive expression of SETD2. The protein expression of SETD2 was associated with clinical stage (P < .001), pathological stage (P < .001), tumor size (P < .001), perinephric fat invasion (P < .001), Eastern Cooperative Oncology Group status (P = .004), surgery type (P < .001), International Society of Urologic Pathologists grade (P < .001), and tumor necrosis (P < .001). SETD2 influenced disease-specific survival (DSS) and overall survival (OS). DSS rates in patients with positive and negative expression of SETD2 were 90.2% and 58.4%, respectively (P < .001). OS rates in patients with positive and negative expression of SETD2 were 87% and 55.4%, respectively (P < .001). In a multivariate Cox analysis, low SETD2 expression was an independent predictor of DSS (hazard ratio [HR], 1.690; 95% confidence interval [CI], 1.0582.700; P = .031) and OS (HR, 1.641; 95% CI, 1.039-2.593; P = .037). CONCLUSION: Our study showed that the negative expression of SETD2 was associated with a worse prognosis, and it was an independent predictor of survival in patients with ccRCC. We believe that the protein expression of SETD2 is an important biomarker in the management of patients with ccRCC.

Immunohistochemical negative expression of ezrin predicts poor prognosis in clear cell renal cell carcinoma.

PURPOSE: To analyze the immunohistochemical expression of ezrin and moesin in clear cell renal cell carcinoma (ccRCC). These proteins, as part of the ezrin-radixin-moesin complex link the cell membrane to the actin cytoskeleton, affecting such processes as cell adhesion, cell survival, cell motility, and signal transduction. Our aim was to examine the impact of their expression on clinical outcomes and survival rates. PATIENTS AND METHODS: Five hundred seventy-five consecutive patients who had been treated surgically for ccRCC in a single center between 1985 and 2016 were selected. A single pathologist reviewed all cases to perform a uniform reclassification and determined the most representative tumor areas for construction of a tissue microarray. RESULTS: Of all ccRCC specimens, 106 (18.3%) were negative for ezrin, and 469 (81.7%) had positive ezrin expression; 16 (2.8%) were negative and 559 (97.2%) were positive for moesin, respectively. Ezrin expression was associated with pT stage (P < 0.001), clinical stage (P = 0.012), synchronic metastasis (P < 0.001), incidental tumors (P = 0.007), and International Society of Urological Pathology histological grade (P = 0.025). There was a correlation between moesin expression and clinical stage (P = 0.027), pT stage (P = 0.025), and pN stage (P = 0.007). Ezrin expression significantly influenced tumor-related deaths. By multivariate analysis, negative ezrin expression was an independent risk factor for disease-specific survival (HR 1.89; 95% CI 1.11-3.20). CONCLUSIONS: Negativity for ezrin in ccRCC patients significantly impacts survival rates. We encourage further prospective studies to analyze ezrin analysis to evaluate its significance in the prognosis of ccRCC.