Exploring Urological Experience in the COVID-19 Outbreak: American Confederation of Urology (CAU) Survey.

PURPOSE: To explore the current situation faced by Latin American urology departments during the COVID-19 Outbreak in terms of knowledge, actions, prioritization of urology practices, and implementation of internal clinical management protocols for inpatients and outpatients. MATERIAL AND METHODS: A non-validated, structured, self-administered, electronic survey with 35 closed multiple choice questions was conducted in Spanish, Portuguese, Italian, and English and Deutsch versions from April 1st to April 30th, 2020. The survey was distributed through social networks and the official American Confederation of Urology (CAU) website. It was anonymous, mainly addressed to Latin American urologists and urology residents. It included 35 questions exploring different aspects: 1) Personal Protective Equipment (PPE) and internal management protocols for healthcare providers; 2) Priority surgeries and urological urgencies and 3) Inpatient and outpatient care. RESULTS: Of 864 surveys received, 846 had at least 70% valid responses and were included in the statistical analyses. Surveys corresponded to South America in 62% of the cases, Central America and North America in 29.7%. 12.7% were residents. Regarding to PPE and internal management protocols, 88% confirmed the implementation of specific protocols and 45.4% have not received training to perform a safe clinical practice; only 2.3% reported being infected with COVID-19. 60.9% attended urgent surgeries. The following major uro-oncologic surgeries were reported as high priority: Radical Nephrectomy (RN) 58.4%, and Radical Cystectomy (RC) 57.3%. When we associate the capacity of hospitalization (urologic beds available) and percentage of high-priority surgery performed, we observed that centers with fewer urological beds (10-20) compared to centers with more urological beds (31-40) performed more frequently major urologic cancer surgeries: RN 54.5% vs 60.8% (p=0.0003), RC 53.1% vs 64.9% (p=0.005) respectively. CONCLUSIONS: At the time of writing (May 13th 2020) our data represents a snapshot of COVID-19 outbreak in Latin American urological practices. Our findings have practical implications and should be contextualized considering many factors related to patients and urological care: The variability of health care scenarios, institutional capacity, heterogeneity and burden of urologic disease, impact of surgical indications and decision making when prioritizing and scheduling surgeries in times of COVID-19 pandemic.

Exploring Urological Experience in the COVID-19 Outbreak: American Confederation of Urology (CAU) Survey

ABSTRACT Purpose: To explore the current situation faced by Latin American urology departments during the COVID-19 Outbreak in terms of knowledge, actions, prioritization of urology practices, and implementation of internal clinical management protocols for inpatients and outpatients. Material and Methods: A non-validated, structured, self-administered, electronic survey with 35 closed multiple choice questions was conducted in Spanish, Portuguese, Italian, and English and Deutsch versions from April 1st to April 30th, 2020. The survey was distributed through social networks and the official American Confederation of Urology (CAU) website. It was anonymous, mainly addressed to Latin American urologists and urology residents. It included 35 questions exploring different aspects: 1) Personal Protective Equipment (PPE) and internal management protocols for healthcare providers; 2) Priority surgeries and urological urgencies and 3) Inpatient and outpatient care. Results: Of 864 surveys received, 846 had at least 70% valid responses and were included in the statistical analyses. Surveys corresponded to South America in 62% of the cases, Central America and North America in 29.7%. 12.7% were residents. Regarding to PPE and internal management protocols, 88% confirmed the implementation of specific protocols and 45.4% have not received training to perform a safe clinical practice; only 2.3% reported being infected with COVID-19. 60.9% attended urgent surgeries. The following major uro-oncologic surgeries were reported as high priority: Radical Nephrectomy (RN) 58.4%, and Radical Cystectomy (RC) 57.3%. When we associate the capacity of hospitalization (urologic beds available) and percentage of high-priority surgery performed, we observed that centers with fewer urological beds (10-20) compared to centers with more urological beds (31-40) performed more frequently major urologic cancer surgeries: RN 54.5% vs 60.8% (p=0.0003), RC 53.1% vs 64.9% (p=0.005) respectively. Conclusions: At the time of writing (May 13th 2020) our data represents a snapshot of COVID-19 outbreak in Latin American urological practices. Our findings have practical implications and should be contextualized considering many factors related to patients and urological care: The variability of health care scenarios, institutional capacity, heterogeneity and burden of urologic disease, impact of surgical indications and decision making when prioritizing and scheduling surgeries in times of COVID-19 pandemic.

Adhesion of renal carcinoma cells to endothelial cells depends on PKCmu.

BACKGROUND: The formation of metastases includes the separation of tumor cells from the primary tumor, cell migration into subendothelial tissue and cell proliferation in secondary organ. In this process, cell adhesion of tumor cells to the endothelium is an essential requirement for formation of metastases. Protein kinase C (PKC) regulates adhesion and proliferation. To identify a relation between PKC isoforms and tumor progression in renal cell carcinoma (RCC), the influence of PKC isoforms on cell adhesion and proliferation, and possible influences of integrins were analyzed in RCC cells. METHODS: The experiments were performed in the RCC cell lines CCF-RC1 and CCF-RC2 after pre-incubation (16 h) with the PKC inhibitors GF109203X (inhibits PKCalpha, betaI, betaII, gamma, delta and epsilon), GO6976 (inhibits PKCalpha, betaI and mu), RO31-8220 (inhibits PKCalpha, betaI, betaII, gamma and epsilon) and rottlerin (inhibits PKCdelta). Cell adhesion was assessed through adherence of RCC cells to an endothelial monolayer. Cell proliferation was analyzed by a BrdU incorporation assay. The expression of beta1 integrins was analyzed by flow cytometry. RESULTS: In CCF-RC1 cells, cell adhesion was significantly reduced by GO6976 to 55% and by RO31-8220 to 45% of control. In CCF-RC2 cells, only GO6976 induced a significant reduction of cell adhesion to 50% of control levels. Proliferation of both cell lines was reduced by rottlerin to 39% and 45% of control, respectively. The beta1 integrin expression on the cell surface of CCF-RC1 and CCR-RC2 cells was decreased by RO31-8220 to 8% and 7% of control, respectively. beta2 and beta3 integrins were undetectable in both cell lines. CONCLUSIONS: The combination of the PKC inhibitors leads to the assumption that PKCmu influences cell adhesion in CCF-RC1 and CCF-RC2 cells, whereas in CCF-RC1 cells PKCepsilon also seems to be involved in this process. The expression of beta1 integrins appears to be regulated in particular by PKCepsilon. Cell proliferation was inhibited by rottlerin, so that PKCdelta might be involved in cell proliferation in these cells.

Regulation of beta1 integrin expression by PKCepsilon in renal cancer cells.

Polarized cell movement represents an essential prerequisite for the progression and metastasis of malignant diseases. Protein kinase C (PKC) which physically associates with integrins has been implicated in the promotion of a migratory cell phenotype. In order to identify a direct link between PKC and integrins in renal cell carcinoma (RCC) the influence of PKC isoforms on integrin expression and possible consequences on proliferation and cell migration was analyzed in RCC cells. The constitutive expression of the PKC isoforms alpha, betaI, betaII, gamma, delta, epsilon, eta, theta, xi, lambda and micro was determined in the RCC cell line CCF-RC1. In addition, the influence of PKC inhibitors RO31-8220, GF109203X and GO6976 on the beta1, beta2 and beta3 integrin expression and cell proliferation of RCC cells was investigated by flow cytometry and by BrdU incorporation, respectively. Furthermore, the motility of CCF-RC1 cells was assessed through chamber chemotaxis analysis. All PKC isoforms tested were expressed in CCF-RC1 cells with the exception of PKClambda and theta. The PKC inhibitor RO31-8220 reduced beta1 integrin expression by 92% and inhibited proliferation by 42% of untreated cells, whereas cell migration remained uninfluenced by RO31-8220. GF109203X and GO6976 reduced beta1 integrin expression to approximately 50% of untreated cells. In contrast, beta2 and beta3 integrins were only weakly affected by RO31-8220, GF109203X and GO6976 treatment. The most significant influence on beta1 integrin expression was obtained by the PKC inhibitor RO31-8220. This leads to the assumption that PKCepsilon is involved in the regulation of beta1 integrin expression. Downregulation of beta1 integrins by RO31-8220 was associated with reduced proliferation, but did not influence migration. These findings provide a conceptual basis for treatment of renal cell carcinoma by interfering with tumor cell proliferation.