Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil.

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.

Extracción renal en donante cadáver: revisión sistemática de la técnica quirúrgica / Deceased donor kidney procurement: systematic review of the surgical technique

Introducción El proceso de extracción renal debe ser una técnica estandarizada con el fin de optimizar las unidades renales para su posterior implante. Objetivos Revisión de la literatura disponible sobre el proceso de extracción renal. Material y métodos Revisión narrativa de la evidencia disponible sobre la técnica de extracción renal en paciente cadáver tras una búsqueda de los manuscritos relevantes indexados en PubMed, EMBASE y SciELO escritos en español e inglés. Resultados La extracción renal en paciente cadáver se divide en dos grupos, tras muerte encefálica (donation after brain death [DBD]) y tras muerte cardiaca (donation after circulatory death [DCD]). La extracción renal en DBD suele acompañarse de la extracción de otros órganos abdominales y/o torácicos, lo que requiere coordinación quirúrgica multidisciplinar. Durante el proceso de extracción debe asegurarse que los pedículos vasculares renales se mantienen íntegros para su posterior implante y disminuir el tiempo de isquemia. Conclusiones La ejecución adecuada y el perfecto conocimiento de la técnica quirúrgica de extracción y de la anatomía, permite disminuir el índice de pérdidas de injertos relacionados con una incorrecta extracción (AU)

Introduction Kidney procurement procedure must be carried out following a standardized technique in order to optimize kidney grafts for their subsequent implantation. Objectives Review of the available literatura on kidney procurement procedure. Material and methods Narrative review of the available evidence on deceased donor kidney procurement technique after a search of relevant manuscripts indexed in PubMed, EMBASE and Scielo written in English and Spanish. Result Deceased donor kidney procurement can be divided into two groups, donation after brain death (DBD) and donation after circulatory death (DCD). Kidney procurement in DBD frequently includes other chest and/or abdominal organs, requiring multidisciplinary surgical coordination. During the harvesting procedure, the renal vascular pedicle must remain intact for subsequent implantation and reduced ischemia time. Conclusions Adequate execution and perfect knowledge of the technique for surgical removal and anatomy reduces the rate of graft losses associated to inadequate harvesting techniques (AU)

Macrophage cell membrane infused biomimetic liposomes for glioblastoma targeted therapy.

Glioblastoma (GBM) is a highly aggressive malignant brain tumor currently without an effective treatment. Inspired by the recent advances in cell membrane biomimetic nanocarriers and by the key role of macrophages in GBM pathology, we developed macrophage membrane liposomes (MML) for GBM targeting. For the first time, it was assessed the role of macrophage polarization states in the effectiveness of these drug delivery systems. Interestingly, we observed that MML derived from M2 macrophages (M2 MML) presents higher uptake and increased delivery of the anticarcinogenic drug doxorubicin compared to M1 macrophage-derived nanocarriers (M1 MML) and control liposomes (CL). Moreover, the lowest uptake by macrophages of MML reveals promising immune escaping properties. Notably, M2 macrophages unveiled a higher expression of integrin CD49d, a crucial protein involved in the bilateral communication of macrophages with tumor cells. Therefore, our findings suggest the potential of using M2 macrophage membranes to develop novel nanocarriers targeting GBM.

Deceased donor kidney procurement: Systematic review of the surgical technique.

INTRODUCTION: Kidney procurement procedure must be carried out following a standardized technique in order to optimize kidney grafts for their subsequent implantation. OBJECTIVES: Review of the available literature on kidney procurement procedure. MATERIAL AND METHODS: Narrative review of the available evidence on deceased donor kidney procurement technique after a search of relevant manuscripts indexed in PubMed, EMBASE and Scielo written in English and Spanish. RESULTS: Deceased donor kidney procurement can be divided into two groups, donation after brain death (DBD) and donation after circulatory death (DCD). Kidney procurement in DBD frequently includes other chest and/or abdominal organs, requiring multidisciplinary surgical coordination. During the harvesting procedure, the renal vascular pedicle must remain intact for subsequent implantation and reduced ischemia time. CONCLUSIONS: Adequate execution and perfect knowledge of the technique for surgical removal and anatomy reduces the rate of graft losses associated to inadequate harvesting techniques.

Nefrectomía parcial y radical laparoscópica en tumores renales cT1. Análisis comparativo de complicaciones y supervivencia / Laparoscopic nephron sparing surgery and radical nephrectomy in cT1 renal tumors. Comparative analysis of complications and survival

Introducción y objetivos: Análisis comparativo de complicaciones postoperatorias y supervivencia entre nefrectomía parcial (NP) y radical (NR) laparoscópica en cáncer de células renales (CCR) cT1.Material y método: Estudio retrospectivo de pacientes birrenos con tumor renal único cT1 tratados en nuestro centro entre los años 2005 y 2018 mediante NP o NR laparoscópica.Resultados: Cumplieron los criterios de inclusión para el estudio 372 pacientes. Fueron tratados mediante NR 156 (41,9%) y 216 (58,1%) mediante NP. En 10 (4,6%) NP y 6 (3,9%) NR hubo complicaciones Clavien Dindo III-V (p = 0,75). El índice de comorbilidad de Charlson (ICC) se identificó como variable predictora independiente de complicaciones (p = 0,02), no influyendo el tipo de cirugía en el análisis multivariante. La estimación de la supervivencia global (SG) fue de 81,2 y de 56,8% a los 5 y 10 años en el grupo de NR y de 90,2 y 75,7% en el grupo de NP, respectivamente (p = 0,0001). Se identificaron como factores predictores de mortalidad global la obesidad (HR 2,77, p = 0,01), el ICC ≥ 3 (HR 3,69, p = 0,001) y el FG<60 mL/min/1,73 m2 al alta (HR 1,87,p = 0,03). El tipo de nefrectomía no demostró influencia en la SG. La estimación de la supervivencia libre de recidiva (SLR) fue de 86,1% a los 5 y 10 años en el grupo de NR y de 93,5 y 83,6% en el grupo de NP respectivamente (p = 0,22).Conclusiones: La NP laparoscópica no es inferior a la NR en términos de seguridad oncológica y quirúrgica en el CCR cT1. El tipo de nefrectomía no influyó en la SG del paciente, sin embargo, sí se comportaron como factores predictores la obesidad, el índice Charlson ≥ 3 y el FG<60 mL/min/1,73 m2 al alta (AU)

Introduction and objectives: Comparative analysis of postoperative complications and survival between laparoscopic partial nephrectomy (PN) and radical nephrectomy (RN) in cT1 renal cell carcinoma (RCC).Material and method: Retrospective study of patients with two kidneys and single renal tumor cT1 treated in our center between 2005 and 2018 by laparoscopic PN or RN.Results: 372 patients met the inclusion criteria for the study. RN was performed in 156 (41.9%) patients and PN in 216 (58.1%). Clavien Dindo III-V complications were observed in 10 (4,6%) PN and 6 (3,9%) RN patients (p = 0.75). The comorbidity Charlson index (CCI) was identified as an independent predictor variable of complications (p = 0.02) and surgical approach did not affect multivariate analysis. Estimated overall survival (OS) was 81.2% and 56.8% at 5 and 10 years in the RN group and 90.2% and 75.7% in the PN group, respectively (p = 0.0001). Obesity (HR 2.77, p = 0.01), CCI ≥ 3 (HR 3.69, p = 0.001) and glomerular filtration rate (GFR) < 60 mL/min/1.73m2 at discharge (HR 1.87, p = 0.03) were identified as predictors of overall mortality. Nephrectomy approach showed no influence on OS. Estimated recurrence-free survival (RFS) was 86.1% at 5 and 10 years in the RN group and 93.5% and 83.6% in the PN group, respectively (p = 0.22).Conclusions: Laparoscopic PN is not inferior to RN in terms of oncologic and surgical safety in cT1 RCC. Nephrectomy approach did not influence patient OS, however, obesity, CCI ≥ 3 and GFR<60 mL/min/1.73m2 at discharge did behave as predictors (AU)

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC-a systematic review and meta-analysis.

BACKGROUND: The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study. METHODS: A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out. All relevant randomized controlled trials appearing in main oncology congresses or in PubMed as of 1 November 2021 were used according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Primarily PFS according to smoking status, and secondarily overall survival (OS) were of interest. Pooled and interaction hazard ratios (HRs) were estimated by fixed or random effects models, depending on the detected degree of heterogeneity. Bias was assessed using the revised Cochrane tool for randomized controlled trials (RoB 2). RESULTS: Information by smoking was available for 1291 patients for PFS (seven studies) and 678 patients for OS (four studies). The risk of bias was low for all studies. Combination treatment significantly prolonged PFS for smokers [n = 502, HR = 0.55, 95% confidence interval (CI): 0.44-0.69] but not for nonsmokers (n = 789, HR = 0.92, 95% CI: 0.66-1.27; treatment-by-smoking interaction P = 0.02). Similarly, a significant OS benefit was found for smokers (n = 271, HR = 0.66, 95% CI: 0.47-0.93) but not for nonsmokers (n = 407, HR = 1.07, 95% CI: 0.82-1.42; treatment-by-smoking interaction P = 0.03). CONCLUSION: In advanced EGFR-non-small-cell lung cancer patients, the addition of an angiogenesis inhibitor to EGFR-tyrosine kinase inhibitor therapy provides a statistically significant PFS and OS benefit in smokers, but not in non-smokers. The biological basis for this observation should be pursued and could determine whether this might be due to a specific co-mutational pattern produced by tobacco exposure.

Laparoscopic nephron sparing surgery and radical nephrectomy in cT1 renal tumors. Comparative analysis of complications and survival.

INTRODUCTION AND OBJECTIVES: Comparative analysis of postoperative complications and survival between laparoscopic partial nephrectomy (PN) and radical nephrectomy (RN) in cT1 renal cell carcinoma (RCC). MATERIAL AND METHOD: Retrospective study of patients with two kidneys and single renal tumor cT1 treated in our center between 2005 and 2018 by laparoscopic PN or RN. RESULTS: 372 patients met the inclusion criteria for the study. RN was performed in 156 (41.9%) patients and PN in 216 (58.1%). Clavien Dindo III-V complications were observed in 10 (4,6%) PN and 6 (3,9%) RN patients (p = 0.75). The comorbidity Charlson index (CCI) was identified as an independent predictor variable of complications (p = 0.02) and surgical approach did not affect multivariate analysis. Estimated overall survival (OS) was 81.2% and 56.8% at 5 and 10 years in the RN group and 90.2% and 75.7% in the PN group, respectively (p = 0.0001). Obesity (HR 2.77, p = 0.01), CCI ≥ 3 (HR 3.69, p = 0.001) and glomerular filtration rate (GFR) <60 mL/min/1.73 m2 at discharge (HR 1.87, p = 0.03) were identified as predictors of overall mortality. Nephrectomy approach showed no influence on OS. Estimated recurrence-free survival (RFS) was 86.1% at 5 and 10 years in the RN group and 93.5% and 83.6% in the PN group, respectively (p = 0.22). CONCLUSIONS: Laparoscopic PN is not inferior to RN in terms of oncologic and surgical safety in cT1 RCC. Nephrectomy approach did not influence patient OS, however, obesity, CCI ≥ 3 and GFR <60 mL/min/1.73 m2 at discharge did behave as predictors.

Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer.

BACKGROUND: At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling. PATIENTS AND METHODS: Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes. RESULTS: Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93). CONCLUSIONS: Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53.

Study of the immunologic response of marine-derived collagen and gelatin extracts for tissue engineering applications.

The host immunologic response to a specific material is a critical aspect when considering it for clinical implementation. Collagen and gelatin extracted from marine sources have been proposed as biomaterials for tissue engineering applications, but there is a lack of information in the literature about their immunogenicity. In this work, we evaluated the immune response to collagen and/or gelatin from blue shark and codfish, previously extracted and characterized. After endotoxin evaluation, bone marrow-derived macrophages were exposed to the materials and a panel of pro- and anti-inflammatory cytokines were evaluated both for protein quantification and gene expression. Then, the impact of those materials in the host was evaluated through peritoneal injection in C57BL/6 mice. The results suggested shark collagen as the less immunogenic material, inducing low expression of pro-inflammatory cytokines as well as inducible nitric oxide synthase (encoded by Nos2) and high expression of Arginase 1 (encoded by Arg1). Although shark gelatin appeared to be the material with higher pro-inflammatory expression, it also presents a high expression of IL-10 (anti-inflammatory cytokine) and Arginase (both markers for M2-like macrophages). When injected in the peritoneal cavity of mice, our materials demonstrated a transient recruitment of neutrophil, being almost non-existent after 24 hours of injection. Based on these findings, the studied collagenous materials can be considered interesting biomaterial candidates for regenerative medicine as they may induce an activation of the M2-like macrophage population, which is involved in suppressing the inflammatory processes promoting tissue remodeling. STATEMENT OF SIGNIFICANCE: Marine-origin biomaterials are emerging in the biomedical arena, namely the ones based in marine-derived collagen/gelatin proposed as cell templates for tissue regeneration. Nevertheless, although the major cause of implant rejection in clinical practice is the host's negative immune response, there is a lack of information in the literature about the immunological impact of these marine collagenous materials. This work aims to contribute with knowledge about the immunologic response to collagen/gelatin extracted from blue shark and codfish skins. The results demonstrated that despite some differences observed, all the materials can induce a macrophage phenotype related with anti-inflammation resolution and then act as immuno-modulators and anti-inflammatory inducible materials.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.

Biomimetic and cell-based nanocarriers - New strategies for brain tumor targeting.

In the last two decades no significant advances were achieved in the treatment of the most frequent and malignant types of brain tumors. The main difficulties in achieving progress are related to the incapacity to deliver drugs in therapeutic amounts into the central nervous system and the associated severe side effects. Indeed, to obtain effective treatments, the drugs should be able to cross the intended biological barriers and not being inactivated before reaching the specific therapeutic target. To overcome these challenges the development of synthetic nanocarriers has been widely explored for brain tumor treatment but unfortunately with no clinical translation until date. The use of cell-derived nanocarriers or biomimetic nanocarriers has been studied in the last few years, considering their innate bio-interfacing properties. The ability to carry therapeutic agents and a higher selectivity towards brain tumors would bring new hope for the development of safe and effective treatments. In this review, we explore the biological barriers that need to be crossed for effective delivery in brain tumors, and the types and properties of cell-based nanocarriers (extracellular vesicles and cell-membrane coated nanocarriers) currently under investigation.

Comparación entre prostatectomía laparoscópica y abierta: análisis de la evolución oncológica / Comparison between laparoscopic and open prostatectomy: Oncological progression analysis

INTRODUCCIÓN: Existe muy poca literatura española que compare resultados oncológicos tras prostatectomía radical (PR) según la vía de abordaje y la metodología es inadecuada. OBJETIVO: Comparar los resultados oncológicos en cuanto a márgenes quirúrgicos (MQ) y recidiva bioquímica (RB) entre PR abierta (PRA) y laparoscópica (PRL). MATERIAL Y MÉTODOS: Comparación de 2 cohortes (307 con PRA y 194 con PRL) entre 2007 y 2015. El estado de los MQ se clasificaron como positivos o negativos y la RB como la elevación del PSA después de la PR > 0,4 ng/ml. Para el contraste de variables cualitativas se utilizó el test Chi-cuadrado y ANOVA para las cuantitativas. Para evaluar los factores predictores de los MQ se ha realizado un análisis multivariante mediante regresión logística. Para evaluar los factores predictores de RB se ha realizado un análisis multivariable mediante regresión de Cox. RESULTADOS: El 43,5% de pacientes tuvieron un Gleason 7 (3 + 4) en la pieza quirúrgica y un 31,7% MQ positivos siendo el estadio patológico más frecuente pT2c en el 61,9%. No existieron diferencias significativas entre ambos grupos, excepto la afectación extracapsular (p = 0,001), más frecuente en la PRL. La mediana de seguimiento fue de 49 meses, evidenciando RB en el 23% de pacientes, sin diferencias significativas entre cohortes. En el análisis multivariable solo el grupo de riesgo D'Amico se comportó como factor predictor independiente de MQ positivos y el score de Gleason y los MQ positivos como factores predictores independientes de RB. CONCLUSIÓN: La vía de abordaje no influyó en el estado de MQ ni en la RB

INTRODUCTION: There are very few Spanish studies that compare oncological outcomes following radical prostatectomy (RP) based on surgical approach, and their methodology is not appropriate. OBJECTIVE: To compare oncological outcomes in terms of surgical margins (SM) and biochemical recurrence (BR) between open radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: Comparison of two cohorts (307 with ORP and 194 with LRP) between 2007-2015. Surgical margin status was defined as positive or negative, and BR as a PSA rise of > 0.4 ng/ml after surgery. To compare the qualitative variables, we employed the Chi-squared test, and ANOVA was used for quantitative variables. We performed a multivariate analysis using logistic regression to evaluate the predictive factors of SM, and a multivariate analysis using Cox regression to evaluate the predictive factors of BR. RESULTS: Gleason 7 (3 + 4) was determined in the surgical specimens of 43.5% of patients, and 31.7% had positive SM. The most frequent pathological stage was pT2c, on the 61.9% of the cases. No significant differences were found between both groups, except for extracapsular extension (p = 0.001), more frequent in LRP. The median follow-up was 49 months. BR was seen in the 23% of patients, without significant differences between groups. In the multivariable analysis, only the D'Amico risk group behaved as an independent predictive factor of positive SM, and Gleason score and positive SM acted as independent predictive factors of BR. CONCLUSION: The surgical approach did not influence SM status or BR

Genomic profiling in non-small-cell lung cancer in young patients. A systematic review.

Lung cancer in young patients is an uncommon and understudied entity that harbors distinctive epidemiological, clinic-demographic, and genomic features. We carried out a systematic review of genomic profiling in young patients with lung cancer from 2010 to 2020 in the main electronic databases and selected 23 manuscripts. Lung cancer in young patients occurs more frequently in women with adenocarcinoma histology and at more advanced stages. Some studies report higher oncogenic genomic alteration in this population, with higher anaplastic lymphoma kinase rearrangements, a distinct profile of epidermal growth factor receptor mutations, and other novel genomic alterations. Although still uncommon, the implementation of next-generation sequencing (NGS) has shed some light on germline genomic alterations associated with lung cancer in young patients. Although outcomes when compared with the older population are conflicting, the overall prognosis is still poor in this subset of patients and efforts to find targetable genomic alterations should be made to improve survival.

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus.

AIM: To stablish a consensus on the treatment strategy for advanced non-small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. METHODS: After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1-9 range scale (1-3 = disagree, 7-9 = agree). Consensus was reached if 2/3 of the participants are in the median range. RESULTS: In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. CONCLUSIONS: A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations.

Comparison between laparoscopic and open prostatectomy: Oncological progression analysis. / Comparación entre prostatectomía laparoscópica y abierta: análisis de la evolución oncológica.

INTRODUCTION: There are very few Spanish studies that compare oncological outcomes following radical prostatectomy (RP) based on surgical approach, and their methodology is not appropriate. OBJECTIVE: To compare oncological outcomes in terms of surgical margins (SM) and biochemical recurrence (BR) between open radical prostatectomy (ORP) and laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: Comparison of two cohorts (307 with ORP and 194 with LRP) between 2007-2015. Surgical margin status was defined as positive or negative, and BR as a PSA rise of >0.4 ng/ml after surgery. To compare the qualitative variables, we employed the Chi-squared test, and ANOVA was used for quantitative variables. We performed a multivariate analysis using logistic regression to evaluate the predictive factors of SM, and a multivariate analysis using Cox regression to evaluate the predictive factors of BR. RESULTS: Gleason 7 (3+4) was determined in the surgical specimens of 43.5% of patients, and 31.7% had positive SM. The most frequent pathological stage was pT2c, on the 61.9% of the cases. No significant differences were found between both groups, except for extracapsular extension (p=0.001), more frequent in LRP. The median follow-up was 49 months. BR was seen in the 23% of patients, without significant differences between groups. In the multivariable analysis, only the D'Amico risk group behaved as an independent predictive factor of positive SM, and Gleason score and positive SM acted as independent predictive factors of BR. CONCLUSION: The surgical approach did not influence SM status or BR.

Prognostic value of neutrophil-to-lymphocyte ratio in advanced cancer patients receiving immunotherapy.

BACKGROUND: The prognostic value of neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in cancer patients. However, the performance of NLR as an early marker of efficacy of immune checkpoint inhibitors (ICI) is still understudied. We studied the utility of NLR at baseline (bNLR), before the second dose of immunotherapy (NLR2) and the NLR trend for predicting efficacy outcomes. METHODS: We included all patients with advanced cancer treated with ICI from June 2013 to April 2019 at La Paz University Hospital, Madrid (Spain). We examined bNLR, NLR2 and NLR trend and explored the association with progression-free survival (PFS) at 6 months, median PFS and overall survival (OS). RESULTS: We included 211 patients. PFS and OS were significantly longer in the low bNLR group than in the high bNLR group [HR 0.71 (95% CI 0.60-0.84) and HR: 0.66 (95% CI 0.55-0.79), respectively]. Regarding NLR2, patients with low NLR2 had significantly longer PFS and OS than patients with high NLR2 [HR 0.67 (95% CI 0.57-0.79) and HR: 0.60 (95% CI 0.50-0.72), respectively]. Finally, for NLR trend, PFS and OS for patients with NLR trend < 1 were significantly longer than those patients with NLR trend ≥ 1 [HR 0.59 (95% CI 0.43-0.82) and HR 0.63 (95% CI 0.44-0.90), respectively]. At the multivariate analysis for PFS and OS, bNLR, NLR2 and NLR trend were all independent prognostic factors for PFS and OS. CONCLUSIONS: bNLR, NLR2 and NLR trends are independent prognostic factors for survival in patients on immunotherapy. The dynamics of NLR in patients on immunotherapy is a promising marker that needs further investigation.

Análisis de supervivencia de los pacientes con cáncer de próstata con factores patológicos desfavorables tratados con prostatectomía radical y radioterapia de rescate tras la recidiva y persistencia bioquímica / Survival analysis of patients with prostate cancer and unfavorable risk factors treated with radical prostatectomy and salvage radiotherapy after biochemical recurrence and persistence

OBJETIVO: Analizar la supervivencia de los pacientes con cáncer de próstata (CP) con factores pronósticos desfavorables (FPD) tratados con PR y radioterapia de rescate (RTR) tras recidiva bioquímica (RB) y persistencia bioquímica (PB). MATERIAL Y MÉTODO: Análisis retrospectivo de 446 pacientes con al menos uno de los siguientes FPD: score de Gleason ≥ 8, estadio patológico ≥ pT3 y/o márgenes quirúrgicos positivos (MQ+). El criterio de RB fue la elevación del PSA por encima de 0,4 ng/ml. Evaluación de supervivencia mediante Kaplan-Meier y log-rank. Para identificar factores de riesgo con posible influencia en la respuesta a RTR y la supervivencia causa-específica (SCE) se usó análisis uni y multivariable (regresión de Cox). RESULTADOS: Mediana de seguimiento: 72 (rango 37-122) meses, mediana de tiempo hasta RB: 42 (rango 20-112) meses. El 36,3% presentaron RB. Presentaron respuesta bioquímica a la RTR 121 (74,7%) pacientes. La supervivencia libre de recaída (SLR) después de la RTR a los 3, 5, 8 y 10 años fue del 95,7, del 92,3, del 87,9 y del 85%, la SG a los 5, 10 y 15 años fue del 95,6, del 86,5 y del 73,5%. La SCE a los 5, 10 y 15 años fue del 99,1, del 98,1 y del 96,6%, respectivamente. Solo el tiempo hasta la RB < 24 meses (HR = 2,55, p = 0,01) se comportó como un factor predictor independiente de SLR después de RTR. CONCLUSIONES: La PR solo consigue control de la enfermedad a los 10años en aproximadamente la mitad de los casos. El tratamiento multimodal secuencial (PR + RTR cuando precise) aumenta este control bioquímico hasta > 87%, lográndose una larga SCE. Los pacientes con un tiempo hasta recidiva > 24 meses respondieron mejor al tratamiento de rescate

OBJECTIVE: Survival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). MATERIALS AND METHODS: Retrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥ 8, pathologic stage ≥ pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4 ng/ml. A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. RESULTS: Mean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients. Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10 years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15 years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15 years were 99.1%, 98.1% and 96.6%. Only time to BR < 24 months (HR = 2.55, P = .01) was identified as an independent risk factor for RFS after SRT. CONCLUSIONS: In these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence > 24 months responded better to rescue treatment

Disección de arteria ilíaca externa con sustitución protésica en trasplante renal / External iliac artery dissection with prosthesis replacement in renal transplantation

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Evaluación de los patrones de recurrencia por grupos de riesgo tras nefrectomía por cáncer renal / Analysis of recurrence trends according to risk groups after renal cancer nephrectomy

INTRODUCCIÓN: No están claramente definidos los patrones de recurrencia tras nefrectomía por cáncer renal. OBJETIVO: Evaluar patrones de recidiva en función del grupo de riesgo de recurrencia (GRR). MATERIAL Y MÉTODO: Análisis retrospectivo de 696 pacientes con carcinoma de células renales tratados con nefrectomía entre 1990-2010. Se definieron tres GRR según la presencia de variables anatomopatológicas (estadio pTpN, grado nuclear, necrosis tumoral [NT], diferenciación sarcomatoide [DS], margen de resección positivo [MR]): -GR bajo (GRB): pT1pNx-0 G1-4, pT2pNx-0 G1-2; no NT, DS y/o MR (+). -GR intermedio (GRI): pT2pNx-0 G3-4;pT3-4pNx-0 G1-2; GRB con NT. -GR alto (GRA): pT3-4pNx-0 G3-4; pT1-4pN+; GRI con NT y/o DS; GRB con DS y/o MR (+). Para el contraste de variables cualitativas se utilizó el test de la Chi cuadrado. El método de Kaplan-Meier se ha utilizado para evaluar la supervivencia libre de recidiva en función de los GRR. Para evaluar diferencias entre las curvas de supervivencia se ha utilizado el test de log-rank. RESULTADOS: La mediana de seguimiento fue de 105 (IQR 63-148) meses. Del total de la serie recidivaron 177 (25,4%) pacientes: 15,9% a distancia, 4,9% local y 4,6% a distancia y local. La tasa de recurrencia varió según el grupo de riesgo con tasas del 72,9% en GRA, 16,9% en GRI y 10,2% en GRB (p = 0,0001). La recurrencia en órgano único fue mayoritaria en el GRB (72,2%) (p = 0,006). El GRB presentó recidiva en forma de metástasis única en el 50% de los casos, frente al 30% y 18,6% en GRI y GRA, respectivamente (p = 0,009). Las localizaciones de recurrencia más habituales fueron pulmón y abdomen. La localización pulmonar predominó en el GRA (72,9%) (p = 0,0001) y la abdominal en el GRB (83,3%) con una tendencia a la significación (p = 0,15). CONCLUSIONES: A medida que aumenta el grupo de riesgo aumentan las recurrencias, sobre todo óseas y pulmonares. En el GRB son más frecuentes las metástasis únicas y en órgano único

INTRODUCTION: Recurrence trends after renal cell cancer nephrectomy are not clearly defined. OBJECTIVE: To evaluate recurrence trends according to recurrence risk groups (RRG). MATERIAL AND METHOD: Retrospective analysis of 696 patients with renal cell cancer treated with nephrectomy between 1990-2010. Three RRG were defined according to the presence of anatomopathological variables (pTpN stage, nuclear grade, tumor necrosis [TN], sarcomatoid differentiation [SD], positive resection margin [RM]): -Low RG (LRG): pT1pNx-0 G1-4, pT2pNx-0 G1-2; no TN, SD and/or RM (+). -Intermediate RG (IRG): pT2pNx-0 G3-4; pT3-4pNx-0 G1-2; LRG with TN. -High RG (HRG): pT3-4pNx-0 G3-4; pT1-4pN+; IRG with TN and/or SD; LRG with SD and/or RM (+). The Kaplan-Meier method has been used to evaluate recurrence-free survival as a function of RRG. The log-rank test was used to evaluate differences between survival curves. RESULTS: The median follow-up was 105 (IQR 63-148) months. Of the total series, 177 (25.4%) patients presented recurrence: distant 15.9%, local 4.9% and 4.6% distant and local. The recurrence rate varied according to the RRG with values of 72.9% for HRG, 16.9% for IRG and 10.2% for LRG (p=.0001). Most cases in LRG presented single organ recurrence (72.2%) (p=.006). The LRG experienced recurrence as single metastasis in 50% of cases, compared to 30% and 18.6% in IRG and HRG, respectively (p=.009). The most common sites of recurrence were lung and abdomen. Lung recurrence predominated in the HRG (72.9%) (p=.0001) and abdominal, in the LRG (83.3%) with a tendency to significance (p=.15). CONCLUSIONS: Recurrence rates (especially bone and lung) increase with higher RG. Single organ recurrences and single metastases are more frequent in LRG

Invasive electrical impedance myography at different levels of contraction of gastrocnemius muscle of rat.

Electrical impedance myography (EIM) is as an experimental technique that associates muscle impedance with muscular activity. Changes in muscle impedance during contraction occur mainly due to changes in the morphological and physiological characteristics of muscles that lead to different impeditivities in comparison with the resting condition. There is no consensus on the details of muscular impedance during muscle activity. EIM measurements on humans are also influenced by factors such as the electrode-skin interface, layers of skin and fat, and the connective tissue that can generate undesirable effects in the impedance signal. These effects can be avoided if EIM measurements are carried out directly on the muscle by using the models of animals. This study investigates changes in the EIM signal in the gastrocnemius muscles of Wistar rats during different levels of muscular contraction. In vivo experiments were conducted on 19 male rats. The muscle was exposed, fixed on a load cell, and electrically stimulated to evoke different levels of muscle contraction. Signals of the components of impedance were analyzed against the muscular force signal. The results show moderate correlations (p < 0.05) among the impedance-related parameters of resistance (r = -0.76), reactance (r = 0.57), and phase (r = 0.53). In addition to providing an experimental protocol for the invasive collection of data on electrical impedance to minimize problems associated with surface electrodes, this study shows that of the components of impedance, resistance is most affected by the intensity of muscular contractions and that morphological changes influence impedance mainly at low intensities.