Prognostic Factors in De Novo Metastatic Renal Cell Carcinoma: A Report From the Latin American Renal Cancer Group.

PURPOSE: To assess the effect of clinical and pathological variables on cancer-specific and overall survival (OS) in de novo metastatic patients from a collaborative of primarily Latin American countries. PATIENTS AND METHODS: Of 4,060 patients with renal cell carcinoma diagnosed between 1990 and 2015, a total of 530 (14.5%) had metastasis at clinical presentation. Relationships between clinical and pathological parameters and treatment-related outcomes were analyzed by Cox regression and the log-rank method. RESULTS: Of 530 patients, 184 (90.6%) had died of renal cell carcinoma. The median OS of the entire cohort was 24 months. American Society of Anesthesiology classification 3-4 (hazard ratio [HR]: 1.64), perirenal fat invasion (HR: 2.02), and ≥ 2 metastatic organ sites (HR: 2.19) were independent prognostic factors for 5-year OS in multivariable analyses. We created a risk group stratification with these variables: no adverse risk factors (favorable group), median OS not reached; one adverse factor (intermediate group), median OS 33 months (HR: 2.04); and two or three adverse factors (poor risk group), median OS 14 months (HR: 3.58). CONCLUSION: Our study defines novel prognostic factors that are relevant to a Latin American cohort. With external validation, these easily discerned clinical variables can be used to offer prognostic information across low- and middle-income countries.

The expression of YWHAZ and NDRG1 predicts aggressive outcome in human prostate cancer.

Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome. Herein, we aimed at identifying molecular biomarkers that could improve risk prediction in PCa. LC ESI-MS/MS was performed on human PCa and benign prostatic hyperplasia (BPH) tissues and peptide data was integrated with omic analyses. We identified high YWHAZ and NDRG1 expression to be associated with poor PCa prognosis considering all Gleason scores (GS). YWHAZ and NDRG1 defined two subpopulations of PCa patients with high and intermediate risk of death. Multivariable analyses confirmed their independence from GS. ROC analysis unveiled that YWHAZ outperformed GS beyond 60 months post-diagnosis. The genomic analysis of PCa patients with YWHAZ amplification, or increased mRNA or protein levels, revealed significant alterations in key DNA repair genes. We hereby state the relevance of YWHAZ in PCa, showcasing its role as an independent strong predictor of aggressiveness.

Characteristics and Surgical Outcomes in Very Elderly Patients (≥75 years) with Renal Cell Carcinoma: Data from the Latin American Renal Cancer Group.

BACKGROUND: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies. OBJECTIVE: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥ 75 years of age. METHODS: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (less than 75 vs. ≥75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications. RESULTS: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p less than 0.01) and higher ASA score (ASA > 2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p less than 0.01), EBL ≥ 500 cc (OR 3.34, p less than 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications. CONCLUSIONS: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities.

Characteristics and Surgical Outcomes in Very Elderly Patients (≥75 years) with Renal Cell Carcinoma: Data from the Latin American Renal Cancer Group

Background: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies. Objective: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥75 years of age. Methods: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (<75 vs.≥ 75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications. Results: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p < 0.01) and higher ASA score (ASA >2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p < 0.01), EBL ≥ 500 cc (OR 3.34, p < 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications. Conclusions: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities. (REV INVEST CLIN. 2020;72(5):308-15)

Small renal masses in Latin-American population: characteristics and prognostic factors for survival, recurrence and metastasis - a multi-institutional study from LARCG database.

BACKGROUND: To evaluate demographic, clinical and pathological characteristics of small renal masses (SRM) (≤ 4 cm) in a Latin-American population provided by LARCG (Latin-American Renal Cancer Group) and analyze predictors of survival, recurrence and metastasis. METHODS: A multi-institutional retrospective cohort study of 1523 patients submitted to surgical treatment for non-metastatic SRM from 1979 to 2016. Comparisons between radical (RN) or partial nephrectomy (PN) and young or elderly patients were performed. Kaplan-Meier curves and log-rank tests estimated 10-year overall survival. Predictors of local recurrence or metastasis were analyzed by a multivariable logistic regression model. RESULTS: PN and RN were performed in 897 (66%) and 461 (34%) patients. A proportional increase of PN cases from 48.5% (1979-2009) to 75% (after 2009) was evidenced. Stratifying by age, elderly patients (≥ 65 years) had better 10-year OS rates when submitted to PN (83.5%), than RN (54.5%), p = 0.044. This disparity was not evidenced in younger patients. On multivariable model, bilaterality, extracapsular extension and ASA (American Society of Anesthesiologists) classification ≥3 were predictors of local recurrence. We did not identify significant predictors for distant metastasis in our series. CONCLUSIONS: PN is performed in Latin-America in a similar proportion to developed areas and it has been increasing in the last years. Even in elderly individuals, if good functional status, sufficiently fit to surgery, and favorable tumor characteristics, they should be encouraged to perform PN. Intending to an earlier diagnosis of recurrence or distant metastasis, SRM cases with unfavorable characteristics should have a more rigorous follow-up routine.

Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia.

BACKGROUND/AIM: Periprostatic adipose tissue (PPAT) directs tumour behaviour. Microenvironment secretome provides information related to its biology. This study was performed to identify secreted proteins by PPAT, from both prostate cancer and benign prostate hyperplasia (BPH) patients. PATIENTS AND METHODS: Liquid chromatography-mass spectrometry-based proteomic analysis was performed in PPAT-conditioned media (CM) from patients with prostate cancer (CMs-T) (stage T3: CM-T3, stage T2: CM-T2) or benign disease (CM-BPH). RESULTS: The highest number and diversity of proteins was identified in CM-T3. Locomotion was the biological process mainly associated to CMs-T and reproduction to CM-T3. Immune responses were enriched in CMs-T. Extracellular matrix and structural proteins were associated to CMs-T. CM-T3 was enriched in proteins with catalytic activity and CM-T2 in proteins with defense/immunity activity. Metabolism and energy pathways were enriched in CM-T3 and those with immune system functions in CMs-T. Transport proteins were enriched in CM-T2 and CM-BPH. CONCLUSION: Proteins and pathways reported in this study could be useful to distinguish stages of disease and may become targets for novel therapies.

Complex relationship between sex hormones, insulin resistance and leptin in men with and without prostatic disease.

OBJECTIVES: To assess sex hormones, leptin and insulin-resistance in men with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and to study associations between androgens and histologic score of prostate tissue in PCa. SUBJECTS AND METHODS: Two hundred ten men older than 45 years selected from 2906 participants of a population screening for PCa were studied: 70 with PCa, 70 with BPH and 70 controls (CG), matched by body mass index and age. Insulin, IGF-1, PSA, leptin, total, free (fT) and bioavailable testosterone (bT) and estradiol were measured. Each group was subdivided into two subgroups considering the presence of metabolic syndrome (MS); androgens and leptin levels were analyzed in the subgroups. RESULTS: Prostate cancer and BPH patients presented higher total, fT and bT levels than CG. IGF-1, insulin and HOMA index were higher in BPH than in the other two groups. PCa presented higher leptin [median (range) 6.5 (1.3-28.0) versus 4.8 (1.1-12.3) ng/ml; p < 0.01] and estradiol [median (range) 37.0 (20-90) versus 29.0 (20-118) pg/ml; p = 0.025] levels than CG. After dividing men considering the presence of MS, leptin was higher and total testosterone was lower in MS patients in all the groups. CONCLUSIONS: It was observed a coexistence of an altered hormone profile with increased sex hormones and leptin in PCa patients, in accordance with the new perspective of PCa pathogenesis.

Human periprostatic adipose tissue: its influence on prostate cancer cells.

BACKGROUND/AIMS: Adipose microenvironment is involved in signaling pathways that influence prostate cancer (PCa) progression. However, the role of human periprostatic adipose tissue (PPAT) from patients with benign prostatic hyperplasia (BPH) has not been studied and compared to that of PPAT from PCa patients. The aim of this paper was to investigate the influence of factors derived from both PPATs on the behavior of androgen-dependent and castration resistant PCa cells. METHODS: PPAT conditioned media (CM) were obtained from tissue samples from patients with clinically primary PCa (TPPAT) or BPH (BPPAT). Cell adhesion, proliferation, migration and metalloproteinase expression were evaluated following exposure of LNCaP (androgen dependent) and PC3 (androgen independent) prostate cancer cell lines to BPPAT or TPPAT CM. RESULTS: Proliferation or motility of LNCaP or PC3 cells were not significantly affected by TPPAT or BPPAT CM. The number of LNCaP but not PC3 cells attached to components of TPPAT CM significantly decreased compared to cells attached to BPPAT CM. PPAT produced and released pro-MMP-9. Zymograms demonstrated that TPPAT CM induced a significant increase in pro-MMP-9 activity compared to BPPAT CM in LNCaP cells but not in PC3 cells. CONCLUSIONS: We conclude that TPPAT released factors, such as pro-MMP-9, could induce the invasive capacity of LNCaP cells and speculate that PPAT derived factors could, in the early stages of prostate cancer, modulate disease progression.

Valoración de las vías de abordaje al riñon en relación al compromiso neuromuscular / Evaluation of the approach routes to kidney regarding the neuromuscular involvement

Se trata de un ejercicio clínico-quirúrgico durante el cual el cirujano, autocriticamente, ensayó y analizó más de 30 incisiones y vías de abordaje, para valorar el diferente compromiso neuromuscular en cirugía renal. Para evaluación de secuelas posquirúrgicas se asoció equilibradamente clínica con EMG regladas. Así sintetizamos como propuesta general, optar por incisiones mínimas, compatibles con la visualización requerida en cada caso, paralelas a las fibras musculares y luego divulsión para ampliar campo. Como conducta fisiátrica de apoyo, ofrecemos un esquema fisiokinésico original, con dos objetivos sincrónicos: resolución dinámica y temprana de las secuelas ya instaladas y prevención de las complicaciones típicas en cirugía renal

Valoración de las vías de abordaje al riñon en relación al compromiso neuromuscular / Evaluation of the approach routes to kidney regarding the neuromuscular involvement

Se trata de un ejercicio clínico-quirúrgico durante el cual el cirujano, autocriticamente, ensayó y analizó más de 30 incisiones y vías de abordaje, para valorar el diferente compromiso neuromuscular en cirugía renal. Para evaluación de secuelas posquirúrgicas se asoció equilibradamente clínica con EMG regladas. Así sintetizamos como propuesta general, optar por incisiones mínimas, compatibles con la visualización requerida en cada caso, paralelas a las fibras musculares y luego divulsión para ampliar campo. Como conducta fisiátrica de apoyo, ofrecemos un esquema fisiokinésico original, con dos objetivos sincrónicos: resolución dinámica y temprana de las secuelas ya instaladas y prevención de las complicaciones típicas en cirugía renal (AU)

Cirugía de rescate en cáncer de testículo / Ranson surgery in testicular neoplasm

Se presentan datos sobre 16 cirugías de rescate en 15 pacientes portadores de tumor de testículo avanzado. Se evalúan los datos de estadificación, evolución y seguimiento. Se efectúan consideraciones sobre la táctica quirúrgica realizada, los hallazgos operatorios y la histología de las piezas resecadas, valorando además la utilidad de los exámenes complementarios

Tumor hamartomatoso del epidídimo: comunicación de un caso / Hamartomatious tumor of the epididymis: report of a case

Se presenta un caso de tumor adenomatoide del epidídimo. Se resalta la rareza del tumor. Se hacen consideraciones sobre la histogénesis y nomenclatura de la lesión

Cirugía de rescate en cáncer de testículo / Ranson surgery in testicular neoplasm

Se presentan datos sobre 16 cirugías de rescate en 15 pacientes portadores de tumor de testículo avanzado. Se evalúan los datos de estadificación, evolución y seguimiento. Se efectúan consideraciones sobre la táctica quirúrgica realizada, los hallazgos operatorios y la histología de las piezas resecadas, valorando además la utilidad de los exámenes complementarios (AU)

Tumor hamartomatoso del epidídimo: comunicación de un caso / Hamartomatious tumor of the epididymis: report of a case

Se presenta un caso de tumor adenomatoide del epidídimo. Se resalta la rareza del tumor. Se hacen consideraciones sobre la histogénesis y nomenclatura de la lesión (AU)