Neutrophil-to-Lymphocyte Ratio Predicts Cancer Outcome in Locally Advanced Clear Renal Cell Carcinoma.

BACKGROUND: To evaluate the association of neutrophil-to-lymphocyte ratio (NLR) with recurrence-free survival (RFS) and overall survival (OS) in patients with locally advanced nonmetastatic clear cell renal cell carcinoma (ccRCC) undergoing radical nephrectomy. MATERIAL AND METHODS: We retrospectively identified 880 nephrectomies performed between January 2009 and December 2016 in a single center, reviewed data from 478 radical nephrectomies for kidney tumors and identified 187 patients with locally advanced nonmetastatic ccRCC (pT3-T4 N0M0). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. OS and RFS were evaluated by the Kaplan-Meier method. Cox proportional-hazards regression models were used to evaluate predictors of RFS and OS. RESULTS: Among 187 patients with ccRCC (mean age 63.4 ± 11.5 years; 118 [63.1%] male), the median follow-up was 48.7 months. On univariate analysis, in patients with Fuhrman nuclear grade of differentiation 3-4, the median time to recurrence was significantly shorter with NLR ≥ 4 than < 4 (24 vs. 55 months, P = .045). On multivariable analysis adjusted for NLR ≥ 4, among all variables analyzed (NLR, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index), only nuclear grade of differentiation was an independent predictor of recurrence (hazard ratio 2.18; 95% confidence interval 1.07-4.92, P = .03). The 3-year OS had no statistically significant difference between patients with NLR ≥ 4 or < 4. CONCLUSION: For patients with locally advanced, nonmetastatic ccRCC, RFS was reduced with high nuclear grade of differentiation and high preoperative NLR. These findings suggest an association between higher NLR and worse outcomes in locally advanced ccRCC.

Evaluation of uro-oncological surgical treatment during the Sars-CoV-2 pandemic in a Brazilian tertiary oncology institution, the new world epicenter

ABSTRACT Introduction: The rapid spread of coronavirus disease 2019 (COVID-19) has dramatic effects on individuals and health care systems. In our institute, a tertiary oncologic public hospital with high surgical volume, we prioritize maintaining cancer treatment as well as possible. The aim of this study is to evaluate if uro-oncological surgeries at pandemic are safe. Materials and Methods: We evaluated patients who underwent uro-oncological procedures. Epidemiological data, information on COVID-19 infection related to surgery and clinical characteristics of non-survival operative patients with COVID-19 infections were analyzed. Results: From 213 patients analyzed, Covid-19 symptoms were noticed in 8 patients at preoperative process or at hospital admission postponing operation; 161 patients were submitted to elective surgery and 44 to emergency surgery. From patients submitted to elective surgeries, we had 1 patient with laboratory confirmation of COVID-19 (0,6%), with mild symptoms and quick discharge. From the urgencies group, we had 6(13%) patients tested positive; 5 were taken to ICU with 4 deaths. Conclusion: Elective uro-oncological procedures at the COVID-19 epidemic period in a COVID-19-free Institute are safe, and patients who need urgent procedures, with a long period of hospitalization, need special care to avoid COVID-19 infection and its outcomes.

Evaluation of uro-oncological surgical treatment during the Sars-CoV-2 pandemic in a Brazilian tertiary oncology institution, the new world epicenter.

INTRODUCTION: The rapid spread of coronavirus disease 2019 (COVID-19) has dramatic effects on individuals and health care systems. In our institute, a tertiary oncologic public hospital with high surgical volume, we prioritize maintaining cancer treatment as well as possible. The aim of this study is to evaluate if uro-oncological surgeries at pandemic are safe. MATERIALS AND METHODS: We evaluated patients who underwent uro-oncological procedures. Epidemiological data, information on COVID-19 infection related to surgery and clinical characteristics of non-survival operative patients with COVID-19 infections were analyzed. RESULTS: From 213 patients analyzed, Covid-19 symptoms were noticed in 8 patients at preoperative process or at hospital admission postponing operation; 161 patients were submitted to elective surgery and 44 to emergency surgery. From patients submitted to elective surgeries, we had 1 patient with laboratory confirmation of COVID-19 (0,6%), with mild symptoms and quick discharge. From the urgencies group, we had 6(13%)patients tested positive; 5 were taken to ICU with 4 deaths. CONCLUSION: Elective uro-oncological procedures at the COVID-19 epidemic period in a COVID-19-free Institute are safe, and patients who need urgent procedures, with a long period of hospitalization, need special care to avoid COVID-19 infection and its outcomes.

Expression of micro-RNAs and genes related to angiogenesis in ccRCC and associations with tumor characteristics.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer in adults. Our aim is to evaluate genes and miRNAs expression profiles involved with angiogenesis and tumor characteristics in ccRCC. METHODS: The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b; 29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-α, VHL, PDGF, VEGF, VEGFR1 and VEGFR2 were analyzed using qRT-PCR in tumor tissue samples from 56 patients with ccRCC. Five samples of benign renal tissue were utilized as control. The expression levels of miRNAs and genes were related to tumor size, Fuhrman nuclear grade and microvascular invasion. RESULTS: miR99a was overexpressed in most samples and its target gene mTOR was underexpressed, this also occurs for miRNAs 106a, 106b, and their target gene VHL. An increase in miR-200b was correlated with high-risk tumors (p = 0.01) while miR-126 overexpression was associated with Fuhrman's low grade (p = 0.03). CONCLUSIONS: Our results show that in ccRCC there are changes in miRNAs expression affecting gene expression that could be important in determining the aggressiveness of this lethal neoplasia.

Predicting necrosis in residual mass analysis after retroperitoneal lymph node dissection: a retrospective study.

BACKGROUND: Recent studies have demonstrated that pathological analysis of retroperitoneal residual masses of patients with testicular germ cell tumors revealed findings of necrotic debris or fibrosis in up to 50% of patients. We aimed at pursuing a clinical and pathological review of patients undergoing post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in order to identify variables that may help predict necrosis in the retroperitoneum. METHODS: We performed a retrospective analysis of all patients who underwent PC-RPLND at the University Hospital of the University of São Paulo and Cancer Institute of Sao Paulo between January 2005 and September 2011. Clinical and pathological data were obtained and consisted basically of: measures of retroperitoneal masses, histology of the orchiectomy specimen, serum tumor marker and retroperitoneal nodal size before and after chemotherapy. RESULTS: We gathered a total of 32 patients with a mean age of 29.7; pathological analysis in our series demonstrated that 15 (47%) had necrosis in residual retroperitoneal masses, 15 had teratoma (47%) and 2 (6.4%) had viable germ cell tumors (GCT). The mean size of the retroperitoneal mass was 4.94 cm in our sample, without a difference between the groups (P = 0.176). From all studied variables, relative changes in retroperitoneal lymph node size (P = 0.04), the absence of teratoma in the orchiectomy specimen (P = 0.03) and the presence of choriocarcinoma in the testicular analysis after orchiectomy (P = 0.03) were statistically significant predictors of the presence of necrosis. A reduction level of 35% was therefore suggested to be the best cutoff for predicting the absence of tumor in the retroperitoneum with a sensitivity of 73.3% and specificity of 82.4%. CONCLUSIONS: Even though retroperitoneal lymph node dissection remains the gold standard for patients with residual masses, those without teratoma in the primary tumor and a shrinkage of 35% or more in retroperitoneal mass have a considerably smaller chance of having viable GCT or teratoma in the retroperitoneum and a surveillance program could be considered.

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer.

BACKGROUND: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). METHODS: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. RESULTS: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). CONCLUSION: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

MMP-9 overexpression due to TIMP-1 and RECK underexpression is associated with prognosis in prostate cancer.

BACKGROUND: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9 and its specific inhibitors, TIMP-1 and RECK, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome in prostate cancer (PC). METHODS: MMP-9, TIMP-1, and RECK expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue specimens collected from 79 patients with clinically localized PC submitted to radical prostatectomy (RP). Frozen benign prostatic tissue from another 10 men with prostate cancer, also submitted to RP, was analyzed to determine if the profile of gene expression was maintained. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). RESULTS: In the tumor samples, MMP-9 was overexpressed by 9.2 times, and TIMP-1 and RECK were underexpressed (0.75 and 0.80 times, respectively). Overexpression of MMP-9 was significantly related to PSA levels above 10 ng/mL (p=0.033). In addition, MMP-9 overexpression was related to biochemical recurrence, with a marginal statistical significance (p=0.089). MMP-9 was also overexpressed in benign tissues of patients with PC, as were TIMP-1 and RECK, in contrast to their underexpression in tumor samples. CONCLUSION: Our results show that MMP-9 is overexpressed and its negative regulators are underexpressed in PC tissue, emphasizing a possible role of MMP-9 in the carcinogenesis process. Additionally, we noticed a relationship between MMP-9 overexpression and increased levels of PSA, an important prognostic factor. In benign tissue adjacent to tumors, the MMP-9 equilibrium is likely maintained because the expression of its negative regulators is preserved.

Tgf-ß1 expression as a biomarker of poor prognosis in prostate cancer.

OBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-ß1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-ß1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-ß1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-ß1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-ß1, a higher expression level was found in patients with Gleason scores ≥ 7 when compared to patients with Gleason scores < 7(p = 0.002). Among the 26 cases of TGF-ß1 overexpression, 92.3% had poor prognostic features. CONCLUSIONS: TGF-ß1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-ß1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-ß1 in prostate carcinogenesis.

Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer

OBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-β1 was underexpressed 67.0 percent of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores >7 when compared to patients with Gleason scores <7(p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3 percent had poor prognostic features. CONCLUSIONS: TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.