Tumor-associated macrophages impair NK cell IFN-γ production and contribute to tumor progression in clear cell renal cell carcinoma.

Tumor-associated macrophages (TAM) are abundant in several tumor types and usually correlate with poor prognosis. Previously, we demonstrated that anti-inflammatory macrophages (M2) inhibit NK cell effector functions. Here, we explored the impact of TAM on NK cells in the context of clear-cell renal cell carcinoma (ccRCC). Bioinformatics analysis revealed that an exhausted NK cell signature strongly correlated with an M2 signature. Analysis of TAM from human ccRCC samples confirmed that they exhibited an M2-skewed phenotype and inhibited IFN-γ production by NK cells. Moreover, human M0 macrophages cultured with conditioned media from ccRCC cell lines generated macrophages with an M2-skewed phenotype (TAM-like), which alike TAM, displayed suppressive activity on NK cells. Moreover, TAM depletion in the mouse Renca ccRCC model resulted in delayed tumor growth and reduced volume, accompanied by an increased frequency of IFN-γ-producing tumor-infiltrating NK cells that displayed heightened expression of T-bet and NKG2D and reduced expression of the exhaustion-associated co-inhibitory molecules PD-1 and TIM-3. Therefore, in ccRCC, the tumor microenvironment polarizes TAM toward an immunosuppressive profile that promotes tumor-infiltrating NK cell dysfunction, contributing to tumor progression. In addition, immunotherapy strategies targeting TAM may result in NK cell reinvigoration, thereby counteracting tumor progression.

Active Surveillance in Prostate Cancer: Current and Potentially Emerging Biomarkers for Patient Selection Criteria.

BACKGROUND: Prostate cancer (PCa) represents one of the most frequent malignancies and the fifth leading cause of cancer death in adult men worldwide. PCa mortality rates have been declining in several Western countries; one of the possible reasons may be related to the application of prostate-specific antigen early detection policies. These early detection protocols increase PCa-specific patient survival; however, a high percentage of these cases corresponds to low-risk PCa that grows very slowly and is unlikely to metastasize to threaten survival. Many low-risk PCa patients receive aggressive therapies, such as radical prostatectomy and radiotherapy, that are costly for patients and/or health systems and generate side effects that affect the quality of life. An alternative to surgery and radiotherapy treatments for low-risk PCa is active surveillance (AS), a strategy based on close disease monitoring and intervention only if the disease progresses. However, proper identification of low-risk PCa patients at the time of diagnosis is essential for the effectiveness AS. The selection of AS candidates remains challenging; thus, effective prognostic biomarkers are needed. SUMMARY: This review article addresses the characteristics of the current and emerging PCa prognostic biomarkers, including tests available for tissue, blood, and urine analyses, for the appropriate selection of PCa patients for AS. In addition, and based on published literature, we performed a selection of potential new biomarkers that can distinguish low-risk PCa. KEY MESSAGES: The literature search yielded four tissue-based tests, two blood-based tests, and six urine-based tests that can be used to determine PCa risk classification. However, most available tests are expensive; thus, cost-effective analyses are needed in order to obtain the approval of government agencies and to be financed by the health systems. Available prognostic urine tests have shown great progress over the last years, and they have the advantage of being minimally invasive; therefore, they may become a routine disease progression test for patients under AS. In addition, new research conducted in the last decade has shown promising biomarkers, including mRNA, miRNA, long noncoding RNA, and metabolites, that could improve existing tests or allow the development of new tools for AS patient selection.

The MICA-NKG2D axis in clear cell renal cell carcinoma bolsters MICA as target in immuno-oncology.

NKG2D is a major natural killer (NK) cell-activating receptor that recognizes eight ligands (NKG2DLs), including MICA, and whose engagement triggers NK cell effector functions. As NKG2DLs are upregulated on tumor cells but tumors can subvert the NKG2D-NKG2DL axis, NKG2DLs constitute attractive targets for antibody (Ab)-based immuno-oncology therapies. However, such approaches require a deep characterization of NKG2DLs and NKG2D cell surface expression on primary tumor and immune cells. Here, using a bioinformatic analysis, we observed that MICA is overexpressed in renal cell carcinoma (RCC), and we also detected an association between the NKG2D-MICA axis and a diminished overall survival of RCC patients. Also, by flow cytometry (FC), we observed that MICA was the only NKG2DL over-expressed on clear cell renal cell carcinoma (ccRCC) tumor cells, including cancer stem cells (CSC) that also coexpressed NKG2D. Moreover, tumor-infiltrating leukocytes (TIL), but not peripheral blood lymphoid cells (PBL) from ccRCC patients, over-expressed MICA, ULBP3 and ULBP4. In addition, NKG2D was downregulated on peripheral blood NK cells (PBNK) from ccRCC patients but upregulated on tumor-infiltrating NK cells (TINK). These TINK exhibited impaired degranulation that negatively correlated with NKG2D expression, diminished IFN-γ production, upregulation of TIM-3, and an impaired glucose intake upon stimulation with cytokines, indicating that they are dysfunctional, display features of exhaustion and an altered metabolic fitness. We conclude that ccRCC patients exhibit a distorted MICA-NKG2D axis, and MICA emerges as the forefront NKG2DL for the development of targeted therapies in ccRCC.

Tumor-Experienced Human NK Cells Express High Levels of PD-L1 and Inhibit CD8+ T Cell Proliferation.

Natural Killer (NK) cells play a key role in cancer immunosurveillance. However, NK cells from cancer patients display an altered phenotype and impaired effector functions. In addition, evidence of a regulatory role for NK cells is emerging in diverse models of viral infection, transplantation, and autoimmunity. Here, we analyzed clear cell renal cell carcinoma (ccRCC) datasets from The Cancer Genome Atlas (TCGA) and observed that a higher expression of NK cell signature genes is associated with reduced survival. Analysis of fresh tumor samples from ccRCC patients unraveled the presence of a high frequency of tumor-infiltrating PD-L1+ NK cells, suggesting that these NK cells might exhibit immunoregulatory functions. In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon direct tumor cell recognition through NKG2D and was further up-regulated by monocyte-derived IL-18. Moreover, in vitro generated PD-L1hi NK cells displayed an activated phenotype and enhanced effector functions compared to PD-L1- NK cells, but simultaneously, they directly inhibited CD8+ T cell proliferation in a PD-L1-dependent manner. Our results suggest that tumors might drive the development of PD-L1-expressing NK cells that acquire immunoregulatory functions in humans. Hence, rational manipulation of these regulatory cells emerges as a possibility that may lead to improved anti-tumor immunity in cancer patients.

Construction of a 3D Surgical Model for Minimally Invasive Partial Nephrectomy: the Urotrainer VK-1.

PURPOSE OF REVIEW: Minimally invasive partial nephrectomy (MIPN) is a very challenging technique and complications may occur during its learning curve. It is important to acquire surgical skills to minimize operative risks. Surgical skills may be acquired through simulation devices or mentoring by a mentor. RECENT FINDINGS: We designed a 3D operable model with multiple and variant surgical scenarios in order to facilitate surgical training in MIPN. The model delivered a real-life feel and handle. To our knowledge, this is the first minimally invasive partial nephrectomy simulator to encompass a series of scenarios with multiple levels of difficulty while delivering a real-life experience.

Minimally Invasive Partial Nephrectomy: Are All Clamps Created Equal? An Ex Vivo Model Simulation of Vascular Clampage.

REASON FOR REVIEW: During the partial nephrectomy, clamping of the vascular pedicle before exision of the tumor is a key step in minimizing blood loss and maintaining adequate visualization. Different vascular clamping devices have been developed for minimal invasive surgery. However, there are no reports comparing them in turn of efficiency RECENT FINDINGS: We present an ex vivo experimental model, designed to demonstrate differences between the clamping devices. All clamps proved to function properly without any leakage at 90 and 120 mmHg, respectively. Our study and the ex vivo model prove that all available clamps are equally efficient at physiologic pressures.

Minimally invasive management of Zinner's syndrome / Manejo mínimamente invasivo del síndrome de Zinner

Abstract Zinner's syndrome (ZS) is a rare congenital malformation of the seminal vesicles and ipsilateral upper urinary tract which is characterized by the triad of ipsilateral ejaculatory duct obstruction, semi nal vesicle cysts, and renal agenesis. We report an 18-year-old male who presented intermittent gross hematuria and hematospermia and ejaculation volume diminution. ZS was diagnosed with magnetic resonance imaging (MRI) of the prostate, among other complementary studies requested. We performed a minimally laparoscopic resection of the left seminal vesicle. The postoperative was uneventful symptoms resolved, and 3 months later semen analysis showed increase in ejaculation volume. Currently, the minimally invasive approach is feasible and effective for the treatment of the seminal vesicle cysts excision in the ZS. We presented a symptomatic patient treated by a laparoscopic approach with successful middle follow-up results.

Resumen El síndrome de Zinner (ZS) es una malformación congénita rara de las vesículas seminales y del tracto urinario superior ipsolateral que se caracteriza por la tríada de obstrucción del conducto eyaculatorio ipsolateral, quistes de vesículas seminales y agenesia renal. Presentamos el caso de un varón de 18 años que presentó hematuria macroscópica intermitente y hemospermia y disminución del volumen de eyaculación. El diagnóstico de ZS se realizó mediante resonan cia magnética (RM) de próstata, entre otros estudios complementarios solicitados. Realizamos una resección mínimamente laparoscópica de la vesícula seminal izquierda. El postoperatorio se resolvió sin complicaciones y 3 meses después el análisis de semen mostró un aumento en el volumen de eyaculación. Actualmente, el abordaje mínimamente invasivo es factible y efectivo para el tratamiento de la escisión de quistes de vesículas seminales en el ZS. Presentamos un paciente sintomático tratado por vía laparoscópica con seguimiento medio exitoso.

[Active surveillance for testicular tumors: adherence and safety.] / Adherencia y seguridad de la vigilancia activa en tumores de testículo.

INTRODUCTION: The active surveillance (AS) of testicular tumors (seminoma and non-seminoma) is the most frequent management option in the stage I disease. Relapses generally occurred within the first 3 years and <5% appear after this time cut-off point is fulfilled. Therefore, the adherence is one of the most important pillars in the AS protocol. The aim of this study is to evaluate the adherence to the AS protocol in a community hospital and, in turn, evaluate the safety of it emphasizing in the relapse-free rate in patients with and without risk factors. MATERIALS AND METHODS: A retrospective study of all the patients included in the AS protocol with seminoma tumors (ST) or non-seminoma tumors (NST) stage I was performed. Postoperative controls were performed according to the NCCN (National Comprehensive Cancer Network) recommendations. Different variables were taken into account, emphasizing in the risk factors: testicular tumor >4cm and the rete testis invasion in the ST, the linfovascular invasion and the percentage>40% of embrionary carcinoma in the NST. Adherence to the AS protocol was evaluated, focusing on those patients who lost it and what time it occurred. RESULTS: A total of 64 patients were included. The median follow-up was 36 months (IC 21-48 months). 12 patients lost the follow-up during the protocol with a median follow-up of 27.5 months (IC 16-30 months). A 21.8% of patients entered in the AS protocol with some associated risk factor. Adherence follow-up was successful in the first year (96.8%) and decreased over time (92.2% at 24 months and 86.3% at 36 months). CONCLUSION: We presented an important adherence to the AS protocol in patients with clinical stage I testicular cancer and in our series there no recurrences after 36 months of follow-up.

INTRODUCCIÓN: La vigilancia activa (VA) de tumores testiculares seminoma (TS) y no-seminomas (TNS) es en la actualidad, la opción de manejo más frecuente utilizada en tumores testiculares estadio clínico I. Las recaídas dentro de este seguimiento se presentan generalmente dentro de los 3 años y <5% se presentan después de este periodo. La adherencia en la VA termina siendo un pilar fundamental.OBJETIVO: El objetivo de este trabajo es evaluar la adherencia al protocolo de vigilancia activa, y a su vez evaluar la seguridad de esta opción de manejo haciendo hincapié en la tasa libre de recaída en pacientes con y sin factores de riesgo.MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo de todos los pacientes incluidos en un protocolo de VA (TS y TNS estadio I). Se tomaron en cuenta diferentes variables, realizando hincapié en la evaluación de los diferentes factores de riesgo, tomando como tal en TS al tamaño testicular > de 4 cm y a la invasión de la rete testis en el resultado anatomopatológico. En cuanto a los TNS, la ILV y un porcentaje >40% de CE fueron los factores de riesgo evaluados. Se evaluó la adherencia al seguimiento del protocolo de VA, haciendofoco en aquellos pacientes que se perdieron del mismo y en qué momento ocurrió.RESULTADOS: Un total de 64 pacientes fueron incluidos a protocolo de VA. La mediana de seguimiento fue de 36 meses (IC 21-48 meses). De todos los pacientes incluidos en este estudio, 12 de ellos perdieron el seguimiento durante el esquema propuesto, presentando una mediana de seguimiento de 27,5 meses (IC 16-30 meses). Un 21,8% de pacientes ingresó al protocolo de VA con algún factor de riesgo asociado. La adherencia al seguimiento fue exitosa en el primer año con un porcentaje de adhesión que alcanzó el 96,8% y fue descendiendo con el paso del tiempo (92,2% a los 24 meses y 86,3% a los 36 meses).CONCLUSIÓN: En nuestra serie, se evidenció una marcada adhesión al protocolo de VA en pacientes con diagnóstico de tumor testicular estadio clínico I, sin registrar recurrencias después de los 36 meses de seguimiento.

Adherencia y seguridad de la vigilancia activa en tumores de testículo / Adherence and safety of active surveillance in testicular tumors

Introducción: La vigilancia activa(VA) de tumores testiculares seminoma (TS) y no-seminomas (TNS) es en la actualidad, la opción de manejomás frecuente utilizada en tumores testiculares estadioclínico I. Las recaídas dentro de este seguimiento sepresentan generalmente dentro de los 3 años y <5% sepresentan después de este periodo. La adherencia en laVA termina siendo un pilar fundamental.Objetivo: El objetivo de este trabajo es evaluar la adherencia al protocolo de vigilancia activa, y a su vezevaluar la seguridad de esta opción de manejo haciendo hincapié en la tasa libre de recaída en pacientescon y sin factores de riesgo. Materiales y métodos: Se realizó un estudio retrospectivo de todos los pacientes incluidos en un protocolode VA (TS y TNS estadio I). Se tomaron en cuenta diferentes variables, realizando hincapié en la evaluaciónde los diferentes factores de riesgo, tomando como talen TS al tamaño testicular > de 4 cm y a la invasiónde la rete testis en el resultado anatomopatológico. Encuanto a los TNS, la ILV y un porcentaje >40% de CEfueron los factores de riesgo evaluados. Se evaluó laadherencia al seguimiento del protocolo de VA, haciendo foco en aquellos pacientes que se perdieron del mismo y en qué momento ocurrió.Resultados: Un total de 64 pacientes fueron incluidosa protocolo de VA. La mediana de seguimiento fue de36 meses (IC 21-48 meses). De todos los pacientesincluidos en este estudio, 12 de ellos perdieron el seguimiento durante el esquema propuesto, presentandouna mediana de seguimiento de 27,5 meses (IC 16-30meses). Un 21,8% de pacientes ingresó al protocolo deVA con algún factor de riesgo asociado.La adherencia al seguimiento fue exitosa en el primeraño con un porcentaje de adhesión que alcanzó el96,8% y fue descendiendo con el paso del tiempo(92,2% a los 24 meses y 86,3% a los 36 meses).Conclusión: En nuestra serie, se evidenció una marcada adhesión al protocolo de VA en pacientes con...(AU)

Introduction: The active surveillance(AS) of testicular tumors (seminoma and non-seminoma)is the most frequent management option in the stageI disease. Relapses generally occurred within the first3 years and <5% appear after this time cut-off pointis fulfilled. Therefore, the adherence is one of the mostimportant pillars in the AS protocol. The aim of this studyis to evaluate the adherence to the AS protocol in acommunity hospital and, in turn, evaluate the safety of itemphasizing in the relapsefree rate in patients with andwithout risk factors.Materials and methods: A retrospective study ofall the patients included in the AS protocol with seminoma tumors (ST) or non-seminoma tumors (NST) stage Iwas performed. Postoperative controls were performedaccording to the NCCN (National ComprehensiveCancer Network) recommendations. Different variableswere taken into account, emphasizing in the risk factors:testicular tumor >4cm and the rete testis invasion in theST, the linfovascular invasion and the percentage>40%of embrionary carcinoma in the NST. Adherence to theAS protocol was evaluated, focusing on those patientswho lost it and what time it occurred.Results: A total of 64 patients were included. Themedian follow-up was 36 months (IC 21-48 months).12 patients lost the follow-up during the protocol with amedian follow-up of 27.5 months (IC 16-30 months). A21.8% of patients entered in the AS protocol with someassociated risk factor.Adherence follow-up was successful in the first year(96.8%) and decreased over time (92.2% at 24 monthsand 86.3% at 36 months).Conclusion: We presented an important adherence to the AS protocol in patients with clinical stage Itesticular cancer and in our series there no recurrencesafter 36 months of follow-up.(AU)

Renal tumor growth rate in patients with previously normal CT scan: Analysis of the initial stage of growth.

OBJECTIVE: Most of the studies regarding natural history of renal masses are based on active surveillance series and suggest that the renal masses have a slow growth rate. Nevertheless, only a few studies report the time between a normal computed tomography (CT) scan to the first detection of a tumor. We aimed to analyze the growth rate in newly diagnosed kidney tumors. MATERIAL AND METHODS: We analyzed patients with enhancing renal masses that developed after a normal CT scan, which was performed at most 12 months earlier. Variables examined included patient age, gender, tumor size, volume, tumor linear growth rate (LGR). All cases were surgically treated. Mann-Whitney U test was used to compare variables. A p<0.05 was considered as statistically significant. RESULTS: We found 31 patients with 33 lesions. Male to female ratio was 1.58 (19/12). The average age was 59.2 years (standard deviation [SD]±12.1), and the mean tumor size was 4.27 cm (SD±4.3). Tumor LGR was 0.87 cm/month (range: 0.28-1.66) and presumed to be 10.4 cm at 1 year (range: 3.36-19.9). Tumor LGR for time detection at <6 month or ≥6 months were 1.1 cm/month and 0.68 cm/month (range: 0.27-1.08 and 0.88-1.76, respectively; p=0.0004), respectively. Tumor LGRs for low- and high-grade tumors were 0.89 cm/month and 0.83 cm/month (p=0.65), respectively. Median volume was 36.1 cm3 (range: 2.61-143.7), and for low and high grade the median volumes were 27.9 cm3 and 47.6 cm3, respectively (p=0.54). Malignant pathology was present in 93.9 % (31 of 33) of masses (lesions). CONCLUSION: We found differences in tumor LGR in tumors detected before and after 6 months. We did not find any correlation between tumor growth rate and Fuhrman grade system, gender, histology, or age. We found the highest LGR published up to date.

PI-RADS 3 lesions: Does the association of the lesion volume with the prostate-specific antigen density matter in the diagnosis of clinically significant prostate cancer?

INTRODUCTION: Currently, a new subclassification of the Pi-RADS 3 lesions and subgroups is being used: 3a (indolent or low-risk lesions with volume <0.5 ml) and 3b (significant or high-risk lesions with volume ≥0.5 ml). The prostate-specific antigen density (PSAd) has been identified as a diagnostic tool that helps to predict clinically significant prostate cancer (csCaP). The aim of this study is to evaluate the association of the volume of the Pi-RADS 3 lesions and the PSAd in the diagnosis of csCaP. MATERIAL AND METHODS: We conducted a retrospective study that included prostate biopsies performed using a transperineal approach and guided by ultrasound between 2015 and 2020. csCaP was defined as Gleason score ≥3 + 4. The population was divided into groups according to the Pi-RADS 3 subclassification and the PSAd value. We calculated sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 3b lesions for the detection of high-grade prostate cancer, alone and combined with PSAD groups. RESULTS: In total, 99 patients with Pi-RADS 3 lesions were included. Forty-three patients were in group 3a and 56, in 3b. Mean PSA was 7.28 ± 2.6 ng/ml. Pi-RADS 3a lesion did not present csCaP but 17.8% of Pi-RADS 3b lesion did. In group 3b with PSAd > 0.15, 62.5% presented csCaP. In those Pi-RADS 3b with PSAd ≤ 0.15, all biopsies were insignificant prostate cancer (isCaP) and 40 biopsies could have been avoided. Considering 3b as positive for csCaP detection, sensitivity was 100%, specificity 48.3%, NPV 17.8%, and PPV 100%. When adding PSAd to group 3b, sensitivity was 100%, specificity was 86.9%, NPV was 62.5%, PPV was 100%. In total, only the subgroup 3b with PSAd > 0.15 presented csCaP and 83.8% biopsies could be avoided. CONCLUSIONS: In this series, the association of the volume of PIRADS 3 lesion and the PSAd improves specificity and PPV contributing to improve the management of csCaP.

[Urinary continence prediction after laparoscopic radical prostatectomy according to preoperative urethral length measurement in multiparametric prostate resonance.] / Predicción de la continencia urinaria post ­ prostatectomía radical laparoscópica utilizando la medición de la longitud uretral en la resonancia multiparamétrica de próstata.

OBJECTIVE: Urinary incontinence (UI) is one of the main complications of radical prostatectomy. Multiple studies have attempted to find factors that may predict early recovery of urinary continence in surgically treated patients. The aim of this study is to evaluate the ability of the length of the membranous urethra (LUM) and the intraprostatic urethra (IUL) measured in preoperative by multiparametric prostate resonance imaging (MRI), to predict post-radical prostatectomy urinary continence. MATERIAL AND METHODS: A retrospective study between 2016 and 2018 was conducted. Patients who under went laparoscopic radical prostatectomy (LRP) and had a previous RMI were included. Different variables were evaluated: age, PSA, BMI, clinical and pathological stage, and the validated questionnaire of urinary incontinence (ICIQ-SF) was performed at 12 months postoperatively. LUM and LUIP were calculated and compared groups (continence vs incontinence) using the Student test (t). A value of p<0.05  was taken as significant. A ROC (Receiver Operating Characteristic) curve was made to predict continence according to LUM and LUIP. RESULTS: Forty-four patients were included. Mean age was 63 years (SD±7.2) and mean PSA was 9.2 ng/dL (SD±5.2). Seventy-five percent presented clinical stageT1c and 43.2% pathological stage pT2cN0. 20.5% (9 patients) presented some degree of UI. The mean LUM was 15.1 mm (SD±5.6) and LUIP 26 mm (SD±10.4). For patients with continence and incontinence, the mean LUM was 18.3 vs 9.5 mm (p=0.0001) and LUIP 31.5vs 15 mm (p=0.0001) respectively. The area under the curve taking as a value of LUM >10mm was 88% and LUIP>20mm was 86.7%. CONCLUSION: The use of preoperative mp RMN measurement of urethral membrane length and intraprostatic urethra may be useful in significantly predicting post-PR urinary continence.

OBJETIVO: La incontinencia de orina (IO) es una de las principales complicaciones de la prostatectomía radical. Múltiples estudios han tratado de encontrar factores para predecir la recuperación temprana de la continencia urinaria en pacientes tratados quirúrgicamente. El objetivo de este trabajo es evaluar la capacidad de la longitud de la uretra membranosa (LUM) y de la uretra intraprostática (LUIP) medida en la resonancia multiparamétrica de próstata (mpRMN) preoperatoria, para predecir la continencia urinaria post-prostatectomía radical. MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo, entre el año 2016 y 2018. Se incluyeron pacientes que fueron sometidos a una prostatectomía radical laparoscópica (PRL) y presentaban una mpRMN previa. Se evaluaron diferentes variables: edad, PSA, IMC, estadio clínico y patológico, y se realizó el cuestionario validado de incontinencia urinaria (ICIQ-SF) a los 12 meses postoperatorios. Se calcularon LUM y LUIP medidas por mpRMN y compararon grupos (continencia vs incontinencia) utilizando el Student test (t). Se tomó un valor de p<0,05 como estadísticametne significativo. Se realizó una curva COR (Característica Operativa del Receptor) para predecir continencia según LUM y LUIP. RESULTADOS: Se incluyeron 44 pacientes. La edad media fue 63 años (DE±7,2) y la media de PSA fue de 9,2 ng/dl (DE±5,2). El 75% presentaron estadio clínico T1c y un 43,2% estadio patológico pT2cN0. La media de LUM fue de 15,1 mm (DE±5,6) y de LUIP 26 mm (DE±10,4). El 20,5% (9 pacientes) presentaba algún grado de IO. Para pacientes con continencia e incontinencia las medias de LUM 18,3 vs 9,5 mm (p=0,0001) y LUIP de 31,5 vs 15 mm (p=0,0001) respectivamente. El área bajo la curva tomando como un valor de LUM >10mm fue del 88% y LUIP >20mm fue de 86,7%. CONCLUSIÓN: La utilización de la medición de la longitud de la uretra membranosa y de la uretra intraprostática por mpRMN preoperatorias, podrían ser útiles para predecir la continencia urinaria post-PR.

Predicción de la continencia urinaria post - prostatectomía radical laparoscópica utilizando la medición de la longitud uretral en la resonancia multiparamétrica de próstata / Urinary continence prediction after laparoscopic radical prostatectomy according to preoperative urethral length measurement in multiparametric prostate resonance

OBJETIVO: La incontinencia de orina (IO) es una de las principales complicaciones de la prostatectomía radical. Múltiples estudios han tratado de encontrar factores para predecir la recuperación temprana de la continencia urinaria en pacientes tratados quirúrgicamente. El objetivo de este trabajo es evaluar la capacidad de la longitud de la uretra membranosa (LUM) y de la uretra intraprostática (LUIP) medida en la resonancia multiparamétrica de próstata (mpRMN) preoperatoria, para predecir la continencia urinaria post-prostatectomía radical. MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo, entre el año 2016 y 2018. Se incluyeron pacientes que fueron sometidos a una prostatectomía radical laparoscópica (PRL) y presentaban una mpRMN previa. Se evaluaron diferentes variables: edad, PSA, IMC, estadio clínico y patológico, y se realizó el cuestionario validado de incontinencia urinaria (ICIQ-SF) a los 12 meses postoperatorios. Se calcularon LUM y LUIP medidas por mpRMN y compararon grupos (continencia vs incontinencia) utilizando el Student test (t). Se tomó un valor de p < 0,05 como estadísticametne significativo. Se realizó una curva COR (Característica Operativa del Receptor) para predecir continencia según LUM y LUIP. RESULTADOS: Se incluyeron 44 pacientes. La edad media fue 63 años (DE ± 7,2) y la media de PSA fue de 9,2 ng/dl (DE ± 5,2). El 75% presentaron estadio clínico T1c y un 43,2% estadio patológico pT2cN0. La media de LUM fue de 15,1 mm (DE ± 5,6) y de LUIP 26 mm (DE ± 10,4). El 20,5% (9 pacientes) presentaba algún grado de IO. Para pacientes con continencia e incontinencia las medias de LUM 18,3 vs 9,5 mm (p = 0,0001) y LUIP de 31,5 vs 15 mm (p = 0,0001) respectivamente. El área bajo la curva tomando como un valor de LUM > 10 mm fue del 88% y LUIP > 20 mm fue de 86,7%. CONCLUSIÓN: La utilización de la medición de la longitud de la uretra membranosa y de la uretra intraprostática por mpRMN preoperatorias, podrían ser útiles para predecir la continencia urinaria post-PR

OBJECTIVE: Urinary incontinence (UI) is one of the main complications of radical prostatectomy. Multiple studies have attempted to find factors that may predict early recovery of urinary continence in surgically treated patients. The aim of this study is to evaluate the ability of the length of the membranous urethra (LUM)and the intraprostatic urethra (IUL) measured in preoperative by multiparametric prostate resonance imaging (MRI), to predict post-radical prostatectomy urinary continence. MATERIAL AND METHODS: A retrospective study between 2016 and 2018 was conducted. Patients who underwent laparoscopic radical prostatectomy (LRP) and had a previous RMI were included. Different variables were evaluated: age, PSA, BMI, clinical and pathological stage, and the validated questionnaire of urinary incontinence (ICIQ-SF) was performed at 12 months postoperatively. LUM and LUIP were calculated and compared groups (continence vs incontinence) using the Student test (t). A value of p < 0.05 was taken as statistically significant. A ROC (Receiver Operating Characteristic) curve was made to predict continence according to LUM and LUIP. RESULTS: Forty-four patients were included. Mean age was 63 years (SD ± 7.2) and mean PSA was 9.2 ng/dL (SD ± 5.2). Seventy-five percent presented clinical stage T1c and 43.2% pathological stage pT2cN0. 20.5% (9 patients) presented some degree of UI. The mean LUM was 15.1 mm (SD ± 5.6) and LUIP 26 mm (SD ± 10.4). For patients with continence and incontinence, the mean LUM was 18.3 vs 9.5 mm (p = 0.0001) and LUIP 31.5 vs 15 mm (p = 0.0001) respectively. The area under the curve taking as a value of LUM >10 mm was 88% and LUIP >20 mm was 86.7%. CONCLUSION: The use of preoperative mpRMN measurement of urethral membrane length and intraprostatic urethra may be useful in significantly predicting post-PR urinary continence

Effectiveness and safety of partial nephrectomy-no ischemia vs. warm ischemia: Systematic review and meta-analysis.

PURPOSE: This study aimed to determine the effectiveness and safety of partial nephrectomy (PN) without ischemia compared with PN with warm ischemia for reducing the deterioration in renal function in patients with cT1 renal tumors. MATERIALS AND METHODS: We conducted a systematic review that included patients over 18 years of age who underwent PN with or without warm ischemia for cT1 renal tumors. The primary outcome was impaired renal function. A search strategy was performed in MEDLINE, EMBASE, LILACS, CENTRAL, the article reference lists, and the unpublished literature to reach saturation of the information. We assessed the risk of bias with the methodological index for nonrandomized studies (MINORS) tool, and we performed a meta-analysis according to the type of variable. RESULTS: We found a total of 5,682 articles, of which 14 met the inclusion criteria. Seven studies evaluated renal function, identifying a difference in means (MD) of 3.50 (95% confidence interval [CI], 1.16 to 5.83), favoring no ischemia. We did not find any significant differences regarding intraoperative bleeding or operative time (MD, 55 mL; 95% CI, -33.16 to 144.08; and MD, 1.87; 95% CI, -20.47 to 24.21; respectively). CONCLUSIONS: In this study, PN without ischemia showed a decrease in deterioration of the estimated glomerular filtration rate compared with warm ischemia.

Value of prostate-specific antigen density in negative or equivocal lesions on multiparametric magnetic resonance imaging.

OBJECTIVE: The prostate-specific antigen density (PSAD) is an accessory tool when suspecting prostate cancer. Multiparametric magnetic resonance imaging (mpMRI) of the prostate has a high rate of false negatives. The aim of this study is to evaluate the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) when adding the PSAD and negative or equivocal mpMRI. MATERIAL AND METHODS: A retrospective study that included prostate biopsies performed using a transperineal approach and guided by ultrasound between 2015 and 2019 was conducted. Clinically significant prostate cancer (csPCa) was defined as Gleason score ≥3+4. The population was divided into groups according to the PSAD level-≤0.15 and >0.15. Sensitivity, specificity, NPV, and PPV of mpMRI were calculated. RESULTS: A total of 292 patients were included; 12.1% (4/33 patients) of the negative mpMRI group presented csPCa, and only 7 in the equivocal mpMRI group presented csPCa. NPV and sensitivity were 91.15% and 90.5%, respectively. In the positive mpMRI group, 53.7% (96/179) had csPCa, with a PPV of 53.6% and specificity of 55.3%. Of the patients with PSAD ≤0.15, 23 (16.54%) presented csPCa. All of them presented a positive mpMRI. All patients with a negative or equivocal mpMRI and a PSAD ≤0.15 presented a clinically non-significant tumor or benign result. The addition of this tool to mpMRI resulted in 100% sensitivity, 69% specificity, and 34.8% PPV. CONCLUSION: In our series, PSAD ≤0.15 increased the NPV in negative or equivocal mpMRI, and through this unnecessary prostate biopsies could be avoided.

Signet ring cell carcinoma of the prostate. Report of 5 cases and literature review. / Carcinoma de próstata en celulas en anillo de sello. Serie de 5 casos y revisión de la literatura.

OBJECTIVE: Signet ring cell carcinoma (SRCC) of the prostate is very a rare tumor. It is comprised of cells that are similar to signet ring cell tumors of the gastrointestinal tract. Diagnosis requires histopathology and also elimination of the adenocarcinomas of other organs. To our knowledge 157 cases have been reported in the literature. MATERIAL AND METHODS: We retrospectively searched in tumor registries from Hospital Aleman de Buenos Aires to identify all prostate cancer since 1990. We analyzed the following variables: age at diagnosis, median prostate-specific antigen (PSA) level, stage, global survival, among others. A review of the literature was done and compared with this series of cases. RESULTS: We identified 5 cases. In our series we found: Mean age 77.8 years (SD 3.2), Median PSA level 18 ng/ml (Range 10.6-331 ng/ml), 3/5 (60%) localized disease and 2/5 (40%) with distant disease at diagnosis. Median survival of 23 months. Comparing with other series we found patients of older age and lower median survival. CONCLUSION: Primary Signet ring cell carcinoma of the prostate is a rare and aggressive histological variant of adenocarcinomas of the prostate. Treatment is the same as classical adenocarcinoma with an emphasis on aggressive multimodal treatment.

OBJETIVO: El carcinoma de células en anillo de sello (CPAS) de la próstata es un tumor muy raro y agresivo. Está compuesto por células que son similares a los tumores de células del anillo de sello del tracto gastrointestinal. El diagnóstico requiere histopatología y también la eliminación de los adenocarcinomas de otros órganos. Hasta donde sabemos se han publicado 157 casos en la literatura.MATERIAL Y MÉTODOS: Realizamos una búsqueda retrospectiva en los registros de tumores del Hospital Alemán de Buenos Aires para identificar todos los tumores de próstata desde 1990. Analizamos las siguientes variables: edad de presentación, mediana de antígeno prostático específico (PSA), estadio oncológico al diagnóstico y supervivencia global entre otras. También se revisó los tratamientos instaurados y se comparó esta serie de casos con la literatura existente. RESULTADOS: Identificamos 5 casos con CPAS. En nuestra serie encontramos: edad promedio de 77,8 años (DE 3,2), mediana de PSA 18 ng/ml (rango 10,6-331 ng/ml), 3/5 (60%) enfermedad localizada y 2/5 (40%) con enfermedad a distancia en el momento del diagnóstico. Mediana de supervivencia de 23 meses. Comparando con otras series encontramos pacientes de mayor edad y menor mediana de supervivencia. CONCLUSIONES: El carcinoma primario de células en anillos de la próstata es una variante histológica rara y agresiva de los adenocarcinomas de próstata. El tratamiento del adenocarcinoma primario de células en anillos de sellos de la próstata es el mismo que el adenocarcinoma clásico con énfasis en el tratamiento multimodal agresivo.

[Partial nephrectomy in mesorrenal tumors greater than 4 cm: 15 years of experience.] / Nefrectomia parcial en tumores mesorrenales mayores de 4 cm: experiencia de 15 años.

OBJECTIVES: Mesorenal tumors (those located in the renal middle line or between both poles) are complex cases for partial nephrectomy (PN). Our objective is to evaluate oncological and perioperative results of PN in these patients with mesorenal tumors greater than 4 cm, mesophytic or endophytic. METHODS: A review of the medical records of patients with tumors with these characteristics operated between January 2016 and June 2016 was performed. RESULTS: 36 cases were included. The mean age was 54.2 years (24-79) with 12 cases of male gender. Mean surgical time: 139 minutes (120-280); 30 cases with complete clamping with mean ischemia of 19 minutes (10-90) and 6 compression of the parenchyma. Mean estimated bleeding: 280 ml (100-900). Mean tumor diameter: 4.3 cm (4.0 to 7.6). Preoperative and postoperative mean glomerular filtration rate 89 ml/min and 76 ml/min (p=0.32) respectively. Median length of stay: 3.8 days (2-21). There were 2 (6.5%) complications (II and IIIb). One case (3.3%) presented positive margin. One patient died due to progression at 14 months. With a median follow-up of 52.1 months (10-168) no recurrences were observed. CONCLUSIONS: We consider that mesorenal tumors, with significant penetration within the renal parenchyma and greater than 4 cm, PN presents both oncological and satisfactory results.

OBJETIVO: Los tumores mesorrenales (aquellos ubicados en la línea media renal o entre ambos polos) son casos complejos para una nefrectomía parcial. Nuestro objetivo es evaluar resultados oncológicos y perioperatorios de NP (nefrectomía parcial) en estos pacientes con tumores mesorrenales mayores a los 4 cm, mesofiticos o endofiticos. METODOS: Se realizó una revisión de las historias clínicas de pacientes con tumores con estas características operados entre enero de 2011 y junio de 2016 y se analizaron distintas variables. RESULTADOS: Se obtuvieron 36 casos. La edad media fue 54,2 años (24-79) con 12 casos de sexo masculino. Tiempo quirúrgico medio: 139 minutos (120- 280); 30 casos con clampeo completo con isquemia media de 19 minutos (10-90) y 6 compresión del parénquima. Sangrado promedio estimado: 280 ml (100-900). Diámetro tumoral medio: 4,3 cm (4,0 a 7,6). Tasa media de filtrado glomerular preoperatoria y posoperatoria 89 ml/min y 76 ml/min (p=0,32) respectivamente. Mediana de internación: 3,8 días (2-21). Hubo 2 (6,5%) complicaciones (II y IIIb). Un caso (3,3%) presentó margen positivo. Un paciente falleció por progresión a los 14 meses. Con una mediana seguimiento de 52,1 meses (10-168) no se observaron recidivas. CONCLUSION: Consideramos que en los tumores mesorrenales, con penetración significativa dentro del parénquima renal y mayores a los 4 cm, la NP presenta resultados tanto oncológicos como funcionales satisfactorios.

Nefrectomia parcial en tumores mesorrenales mayores de 4 cm: experiencia de 15 años / Partial nephrectomy in mesorrenal tumors greater than 4 cm: 15 years of experience

Objetivo: Los tumores mesorrenales (aquellos ubicados en la línea media renal o entre ambos polos) son casos complejos para una nefrectomía parcial. Nuestro objetivo es evaluar resultados oncológicos y perioperatorios de NP (nefrectomía parcial) en estos pacientes con tumores mesorrenales mayores a los 4 cm, mesofiticos o endofiticos. Metodos: Se realizó una revisión de las historias clínicas de pacientes con tumores con estas características operados entre enero de 2011 y junio de 2016 y se analizaron distintas variables. Resultados: Se obtuvieron 36 casos. La edad media fue 54,2 años (24-79) con 12 casos de sexo masculino. Tiempo quirúrgico medio: 139 minutos (120- 280); 30 casos con clampeo completo con isquemia media de 19 minutos (10-90) y 6 compresión del parénquima. Sangrado promedio estimado: 280 ml (100-900). Diámetro tumoral medio: 4,3 cm (4,0 a 7,6). Tasa media de filtrado glomerular preoperatoria y posoperatoria 89 ml/min y 76 ml/min (p = 0,32) respectivamente. Mediana de internación: 3,8 días (2-21). Hubo 2 (6,5%) complicaciones (II y IIIb). Un caso (3,3%) presentó margen positivo. Un paciente falleció por progresión a los 14 meses. Con una mediana seguimiento de 52,1 meses (10-168) no se observaron recidivas. Conclusión: Consideramos que en los tumores mesorrenales, con penetración significativa dentro del parénquima renal y mayores a los 4 cm, la NP presenta resultados tanto oncológicos como funcionales satisfactorios

Objectives: Mesorenal tumors (those located in the renal middle line or between both poles) are complex cases for partial nephrectomy (PN). Our objective is to evaluate oncological and perioperative results of PN in these patients with mesorenal tumors greater than 4 cm, mesophytic or endophytic. Methods: A review of the medical records of patients with tumors with these characteristics operated between January 2016 and June 2016 was performed. Results: 36 cases were included. The mean age was 54.2 years (24-79) with 12 cases of male gender. Mean surgical time: 139 minutes (120-280); 30 cases with complete clamping with mean ischemia of 19 minutes (10-90) and 6 compression of the parenchyma. Mean estimated bleeding: 280 ml (100-900). Mean tumor diameter: 4.3 cm (4.0 to 7.6). Preoperative and postoperative mean glomerular filtration rate 89 ml/min and 76 ml/min (p = 0.32) respectively. Median length of stay: 3.8 days (2-21). There were 2 (6.5%) complications (II and IIIb). One case (3.3%) presented positive margin. One patient died due to progression at 14 months. With a median follow-up of 52.1 months (10-168) no recurrences were observed. Conclusions: We consider that mesorenal tumors, with significant penetration within the renal parenchyma and greater than 4 cm, PN presents both oncological and satisfactory results

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.