Prognostic role of the immunohistochemical expression of proteins related to the renin-angiotensin system pathway in nonmetastatic clear cell renal cell carcinoma.

INTRODUCTION: Stage migration has been observed in renal cell carcinoma (RCC) in recent decades; however, mortality rates have continuously increased in some countries. Tumoral factors have been characterized as major predictors of RCC. Nonetheless, this concept can be improved by combining these tumoral factors with other variables, including biomolecular factors. PURPOSE: This study aimed to assess the immunohistochemical (IHC) expression and prognostic value of renin (REN), erythropoietin (EPO), and cathepsin D (CTSD), and to evaluate whether the concomitant expression of these markers can influence the prognostic outcomes in patients without metastasis. MATERIAL AND METHODS: In total, 729 patients with clear cell RCC (ccRCC) who underwent surgical treatment between 1985 and 2016 were evaluated. All the cases in the tumor bank were reviewed by dedicated uropathologists. The IHC expression patterns of the markers were assessed using a tissue microarray. REN and EPO were classified as "positive" or "negative" expression. CTSD was grouped into "absent or weak expression" or "strong expression." Associations between clinical and pathological variables and the studied markers, in addition to 10-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival rates, were described. RESULTS: REN and EPO expressions were positive in 70.6% and 86.6% of patients, respectively. Absent or weak and strong expressions of CTSD were observed in 58.2% and 41.3% of the patients, respectively. EPO expression had no impact on survival rates even when assessed concomitantly with REN. Negative REN expression was associated with advanced age, preoperative anemia, larger tumors, perirenal fat, hilum or renal sinus infiltration, microvascular invasion, necrosis, high nuclear grade, and clinical stages III to IV. In contrast, strong CTSD expression was associated with poor prognostic variables. The expression patterns of REN and CTSD were unfavorable predictors of the 10-year OS and CSS. In particular, the combination of negative REN and strong CTSD expression had a negative impact on these rates, including a higher risk of recurrence. CONCLUSION: Loss of REN expression and strong CTSD expression were independent prognostic factors in nonmetastatic ccRCC, particularly when the concomitant expression pattern of both markers was present. EPO expression did not influence survival rates in this study.

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

ABSTRACT 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.

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.

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.

Completely endophytic renal tumor: A laparoscopic approach.

Kidney cancer is the third most common urologic malignancy and a 2% annual increase in the incidence has occurred over the past two decades, largely because of the increased utilization of imaging. The majority of these tumors are small, so the indications for nephron-sparing surgery and for minimally invasive surgery are continually expanding. Complex kidney lesions, such as those completely endophytic, are still a challenge even for experienced surgeons. Our objective is to demonstrate the operative technique for laparoscopic partial nephrectomy with the aid of intra-operative ultrasound in a man with a totally endophytic renal lesion. Case: A 52 years old man, asymptomatic, with incidental renal mass of 2.9 cm, completely endophytic (R.E.N.A.L score 9p) submitted to partial laparoscopic nephrectomy. Surgical time was 2 hours, with 20 minutes of ischemia. Pathological anatomy confirmed tumor of clear cells T1a, free margins.

Continent vesicovaginal fistula.

Vesicovaginal fistula is an abnormal communication between the bladder and vagina and represents the most frequent type of fistula in the urinary tract. The most common cause in Brazil is iatrogenic fistula, secondary to histerectomia. Classically these women present continuous urinary leakage from the vagina and absence of micturition, with strong negative impact on their quality of life. We present a case of totally continent vesicovaginal fistula, with a follow-up of 11 years with no complications.

Fístula vesicovaginal continente / Continent vesicovaginal fistula

A fístula vesicovaginal é uma comunicação anormal entre a bexiga e a vagina, sendo o tipo mais comum de fístula do trato urinário. A causa mais frequente no Brasil é a iatrogênica, secundária à histerectomia. Classicamente, as mulheres nessa condição, apresentam perda urinária contínua pela vagina e ausência de micção, com forte impacto negativo na qualidade de vida. Apresentamos um caso de fístula vesicovaginal totalmente continente, com seguimento de 11 anos, sem complicações.

Vesicovaginal fistula is an abnormal communication between the bladder and vagina and represents the most frequent type of fistula in the urinary tract. The most common cause in Brazil is iatrogenic fistula, secondary to histerectomia. Classically these women present continuous urinary leakage from the vagina and absence of micturition, with strong negative impact on their quality of life. We present a case of totally continent vesicovaginal fistula, with a follow-up of 11 years with no complications.