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.

Dusting efficacy between the regular setting of holmium laser (Ho:YAG) versus Vapor Tunnel pulse modality for non-complex kidney stones.

The new pulse modality Vapor-Tunnel™ (VT) consists of a very long pulse that uses the minimum peak power, causing the energy to pass through a previously created vapor channel or tunnel. The first part of the pulse creates a vapor channel, whereas the remaining energy is discharged immediately after, passing straight through the previously created tunnel. The aim of this study is to compare the dusting efficacy between Ho:YAG laser with long pulse and Ho:YAG laser with VT for non-complex kidney stones. A retrospective comparative study of 236 patients who underwent retrograde intrarenal surgery using Ho:YAG laser (long pulse vs. VT) was performed. Stone size, stone density, laser settings, laser emission time, and total operative time were recorded. We also assessed the lithotripsy efficacy (J/mm3). The stone-free rate was defined as the absence of stone fragments in a non-contrast abdominal computed tomography 4 weeks after the procedure. A total of 118 patients were included in each group. There was no significant difference in age, gender, and body mass index. Median stone volume (737 mm3 vs. 636 mm3) and stone density (788 HU vs. 656 HU) were higher in the VT group. Total energy used (14.5 J vs. 18.2 J), the laser emission time (20 min vs. 26 min), and the total operative time (79.5 min vs. 95 min) were significantly lower in the VT group. The stone-free rate was comparable between both groups (74.5% for VT and 66.1% for the long-pulse group, p = 0.15). When we evaluated the efficacy of laser lithotripsy, a significantly lower difference was obtained in the VT group (median 12.5 J/mm3 vs. median 23.1 J/mm3). The VT pulse modality was associated with decreased laser time and operative time. Additionally, it increased lithotripsy efficacy compared to Ho:YAG long pulse laser, but with a comparable free-stone rate.

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.

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.

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.

Urinary manifestations in Isaacs's syndrome. Our experience in 8 cases.

INTRODUCTION: Isaacs's syndrome (IS), is a rare neurological disorder, characterized by sustained muscular activity, fasciculations, cramps, myokymia, excessive sweating, and occasional elevation of creatine phosphokinase (CPK) enzyme. AIM: To report our experience in patients with IS and urinary manifestations, describing clinical findings, test's results, and response to treatment. Methods An observational, retrospective analysis of patients with IS and urinary manifestations treated at German Hospital of Buenos Aires between 2001 and 2011 was done. Diagnosis was performed with clinical examination and electromyography (EMG) of external sphincter of the anus and/or urethra. Demographic, clinical, and treatment variables were analyzed. International Prognostic Scoring System (IPSS) at diagnosis and follow up was made. RESULTS: Eleven IS patients were recruited, of whom 8 (72.72%) were females with a mean age 47.87 years (DS ± 13.95) and presented associated lower tract urinary symptoms (LUTS). Six of them (75%) had voiding and 2 (25%) filling symptoms. Urodynamic and electromyographic findings reproduced symptomatology in all patients. Patients with voiding symptomatology were treated with combination of alpha-blockers with benzodiazepines; membrane stabilizings agents; antiepileptics; neurotropic; corticoids; posterior tibial nerve stimulation and botulinum toxin, achieving improvement in 4/6. The two patients with storage symptoms were treated in first instance with anticholinergic drugs, one of which did not respond completely was added oral pentosansulfate and electrical stimulation, reversing the symptomatology. Four patients had associated pathologies: Hashimoto's thyroiditis; Sjögren's syndrome; dysautonomia, and myasthenia gravis. CONCLUSIONS: In our experience, IS urinary manifestations are common and usually has a good evolution with adequate treatment for each patient.

Laparoscopic resection of isolated fossa recurrence of renal cell carcinoma after open nephrectomy: report of 6 cases and literature review.

OBJECTIVES: Local recurrence after a correct surgical technique and absence of distant metastasis is a rare occurrence after radical nephrectomy. Surgical resection remains the standard management for this pathological setting. Nevertheless controversy persists over surgical approach and adjuvant treatments. METHODS: We report on perioperative outcomes of a small multi-institutional series of patients with fully laparoscopic management of isolated renal fossa recurrence following open radical nephrectomy. RESULTS: All patients underwent full laparoscopic surgery. Mean operative time was 140 minutes (range 75 to 240 minutes). Only one patient had a Clavien Grade IIIa complication. Mean hospital stay was 3 days (range 2 to 4 days). Out of the six patients, 5 had a mean follow-up of 20 months (range 9 to 32 months). Only one of these patients evolved with distant metastasis after surgery. CONCLUSIONS: Laparoscopic resection of local recurrence after open radical nephrectomy is a challenging but reproducible technique. There is still no consensus or an operative protocol for this clinical setting. However, as long as surgery is kept within the possibilities, a laparoscopic approach should be sought.

Seminal vesicle leiomyosarcoma: Case report and literature review.

INTRODUCTION AND BACKGROUND: Primary leiomyosarcoma of the seminal vesicle is an extremely rare and highly malignant disease with less than 15 cases reported. CASE DESCRIPTION: A 34-year-old man presented with acute urinary symptoms. Imagen studies showed an abdominal mass (80 mm × 65 mm × 50 mm) with contrast enhancement, compressing the right side of the bladder but with a clear cleavage level between surrounding organs. The patient underwent a transrectal US-guided biopsy which was informed as compatible with leiomyosarcoma by immunohistochemical characterization. We performed a cystoprostatectomy and pelvic lymphadenectomy plus radiotherapy. Pathology showed a 7.5 cm × 6 cm nodular para-vesical Leiomyosarcoma histological grade 2 with 0/22 lymph nodes involved. Twelve months after the surgery no recurrences have presented. CONCLUSION: A multi-disciplinary therapeutic approach, combined with close follow-up, is mandatory to obtain good outcomes in such rare and challenging cases.

Hemoperitoneum after transperineal prostate biopsy.

Bleeding is the most common complication after a prostate biopsy, commonly self-limited. We describe a case of a patient who developed a hemoperitoneum after a transperineal prostate biopsy. A 65-year-old man with a history of prostate cancer diagnosed in 2016 by transurethral resection, with no further urologic control until 2020 when a rise in the serum prostate-specific antigen was diagnosed: 4.49 ng/ml. Prostate digital rectal examination had no pathologic findings. Magnetic resonance imaging informed anequivocal lesion. A target transperineal fusion biopsy was performed, guided by ultrasound (US). Pre-surgical blood tests, including coagulogram, were normal. No immediate postoperative complications were recorded, and the patient was discharged. Hours later, he returned after a head concussion due to orthostatic hypotension and diffuse abdominal pain. Blood test showed a drop in hematocrit and hemoglobin values. Abdominal US and abdominopelvic computed tomography scan showed free intraperitoneal fluid and intraperitoneal hematic collection on top of the bladder of 104 × 86 mm with no active bleeding. The patient was admitted to intensive care unit due to persistent hypotension despite fluid restoration. He received a single-unit blood transfusion and had a good response to vasopressors. Abdominal pain decreased. He was finally discharged with stable hematocrit 48hours after admission. Clinical management with no surgery or radiologic angio-embolization was required. We found no clear origin of the intraperitoneal bleeding, but we hypothesize that maybe the previous transurethral resection of the prostate made anatomical changes that facilitated blood passage to the abdominal cavity after puncture of branches from the inferior vesical artery.

La complicación más frecuente tras una biopsia prostática es el sangrado, generalmente autolimitado. Aquí describimos un caso de hemoperitoneo secundario a dicho procedimiento. Hombre de 65 años con antecedentes de cáncer de próstata diagnosticado en 2016 por una resección transuretral de próstata, sin seguimiento urológico, consultó en 2020 por aumento del antígeno prostático específico: 4.49 ng/ml, asociado a tacto rectal normal y una resonancia multiparamétrica de próstata mostró una lesión indeterminada. Se realizó una biopsia prostática transperineal por fusión guiado por ecografía. Los análisis preoperatorios, incluido coagulograma, eran normales. No se registraron complicaciones intraquirúrgicas y se indicó el alta. Horas más tarde, consultó al hospital por hipotensión ortostática y dolor abdominal difuso. Los análisis demostraron caída del hematocrito y hemoglobina. Una ecografía y posterior tomografía computada evidenciaron una colección supravesical de 104 × 86mm sin signos de sangrado activo. Se indicó internación en sala de cuidados intensivos debido a hipotensión refractaria a expansiones con requerimiento de vasopresores. Recibió una transfusión de glóbulos rojos. Por favorable evolución, 48 horas después del ingreso recibió el alta. En este caso, fue posible un manejo conservador, sin requerimiento de cirugía o embolización. Si bien no se encontró sitio exacto del sangrado, creemos que la resección transuretral previa podría haber generado cambios anatómicos que facilitaran el pasaje de sangre, posiblemente proveniente de ramas de la arteria vesical inferior a cavidad abdominal luego de la punción.

[Risk factors for contrast extravasation in renal colic]. / Factores de riesgo para extravasación de contraste en cólico renal.

INTRODUCTION: Non-traumatic ruptureof the pyeloureterocaliceal system (PUC) is anuncommon clinical entity. The most frequent cause isureteral obstruction due to lithiasic pathology, whichis present in up to 75%. To our knowledge, there isno description in the literature of the possible factorsassociated with this event. Our objective is to analyzethe variables associated with intravenous contrastextravasation in patients with renal colic due to singleureteral lithiasis. MATERIALS AND METHODS: We performed aretrospective, descriptive analysis of a series ofpatients who, in the context of renal colic, presentedendovenous contrast extravasation throughthe urinary system in computed tomography (CT).Patients with single ureteral lithiasis without otherassociated pathology were included. A comparisonof the samples from the group with contrast leakage(group 1) with an equal number of consecutiveCT scans without contrast leakage (group 2) in patientswith renal colic lithiasis was performed in alogistic regression model to identify risk factors forcontrast leakage. RESULTS: There were 117 cases of contrast leakagefrom January 2013 to July 2018. Eighty-sixpercent of the lithiases were 5 mm and 79% werelocated in the lower ureter. 72% of patients presentedwith intrarenal pelvis. In the univariate analysisboth location in lower ureter, lithiasis 5 mm, andintrarenal pyelic anatomy increased the probabilityof extravasation. In multivariate model, 5 mmlithiasis increased five times the risk of extravasationcompared to larger ones, the location in distalureter increased three times and the anatomy withintrarenal pelvis increased two times compared toother location and extrarenal pelvis, respectively, ina statistically significant way the risk of presentingcontrast leakage. CONCLUSION: In this series, we found an increasedrisk of contrast leakage in a lithiasic renalcolic in patients with intrarenal pelvic anatomy,with lithiasis less than or equal to 5 mm and locatedin the lower ureter.

INTRODUCCIÓN: La ruptura no traumaticadel sistema pieloureterocalicial (PUC) es una entidadclínica poco común. La causa más frecuente esla obstrucción ureteral por patología litiásica, que sepresenta hasta en un 75%. A nuestro conocimiento, noexiste en la literatura una descripción de los posiblesfactores asociados con este evento. Nuestro objetivo esanalizar las variables asociadas con la extravasaciónde contraste endovenoso en pacientes con cólico renalpor litiasis ureteral única.MATERIALES Y MÉTODOS: Se realizó un análisis retrospectivo,descriptivo, de una serie de pacientes que,en contexto de cólico renal, presentaron extravasaciónde contraste endovenoso por el sistema urinario entomografía computada (TC). Se incluyeron pacientescon litiasis ureteral única sin otra patologia asociada.Se realizó una comparación de las muestras del grupocon fuga de contraste (grupo 1) con igual número detomografías consecutivas sin fuga de contraste (grupo2) en paciente con cólico renal litiásico, en un modelode regresión logística para identificar factores de riesgode fuga de contraste. RESULTADOS: Se registraron 117 casos de fuga decontraste desde enero de 2013 hasta julio de 2018. El86% de los litos fueron ≤ 5 mm y el 79 % se ubicaronen uréter inferior. El 72% de los pacientes presentópelvis intrarrenal. En el análisis univariado tanto ubicaciónen uréter inferior, litiasis ≤ 5 mm, como anatomíapielica intrarrenal aumentaron la probabilidad deextravasación. En el modelo multivariado, litiasis ≤ 5mm aumentaron cinco veces el riesgo de extravasacióncomparado con las mayores, la ubicación en uréterdistal aumentó en tres veces y la anatomía con pelvisintrarrenal aumentó en dos veces comparado conotra ubicación y pelvis extrarrenal, respectivamente,de manera estadísticamente significativa el riesgo depresentar fuga de contraste.CONCLUSIÓN: En esta serie, encontramos aumentode riesgo de fuga de contraste en un cólico renal litiásicoen pacientes con anatomía piélica intrarrenal,con litos menores o iguales a 5 mm y ubicados enuréter inferior.

[Moderate/severe hydronephrosis before ureteral double-j stent insertion is associated with less back pain during micturition.] / La hidronefrosis moderada/severa antes de la inserción del catéter ureteral doble J se asocia con menos dolor de espalda durante la micción.

OBJECTIVE: Symptoms related toureteral double-J stent are the most common complaintamong patients. Back pain during micturition isone of the most frequent but intensity and durationmay vary between them. This study aimed to assessthe relationship between hydronephrosis grade beforeureteral double-j stent insertion and back pain duringmicturition. PATIENTS AND METHODS: All consecutive patientsundergoing a ureteral double-j insertion secondaryto urolithiasis between 2017 and 2019 were prospectivelyenrolled. Hydronephrosis was assessed using aCT scan and was categorized according to renal pelvismeasure as 0-10 mm (low group), and ≥10 mm(moderate group). At one week postoperative, patientsymptoms were evaluated using the Spanish validatedversion of the Ureteral Stent Symptom Questionnaire(USSQ) and 10 cm visual analog scale (VAS). Meanscores for USSQ domains and mean VAS scores werecompared. RESULTS: 149 patients were included and evaluated.The mean age was 48.2±15.1 years. We found no significantdifferences in mean scores for each main domainin the USSQ or VAS. The presence of flank painduring micturition was present in 73.5% and 52.5 %for the low vs moderate hydronephrosis group respectively(p=0.01). Sub-analysis by gender was 78.7 % vs44.0 % (p=0.00) and 58.6% vs 66.6% (p=0.6) of low andmoderate group in men and women respectively.Analysis of the USSQ item score revealed thatthe moderate hydronephrosis group presented less''pain or discomfort when urinating,'' less ''presenceof back pain when urinating,'' less ''admission orprocedure because of discomfort,'' and less ''feelingabout reinsertion''. CONCLUSION: Patients in the moderate hydronephrosisgroup did not have significant advantagesin terms of voiding symptoms, pain, general health,sexual matters, or additional problems determined bythe USSQ or in VAS. However, sub-analysis reportedadvantages concerning pain and additional questions.Men with moderate hydronephrosis presented statisticallysignificantly less pain during micturition.

INTRODUCCIÓN Y OBJETIVO: Lossíntomas relacionados con el catéter ureteral doble-Json la queja más común en los pacientes. El dolor deespalda durante la micción es uno de los más frecuentes,pero la intensidad y la duración varían entre ellos.El objetivo de este estudio fue evaluar la relación entreel grado de hidronefrosis antes de la inserción del catéterureteral doble-J y el dolor de espalda durante lamicción. PACIENTES Y MÉTODOS: Se incluyeron prospectivamentetodos los pacientes consecutivos que sesometieron a la inserción de un catéter ureteral doblej debido a la urolitiasis entre 2017 y 2019. La hidronefrosisse evaluó mediante una tomografía computarizaday se clasificó según la medida de la pelvis renalcomo 0-10 mm (grupo bajo), y ≥10 mm (grupo moderado/severo). Una semana después de la operación,los síntomas del paciente se evaluaron utilizando laversión validada en español del Cuestionario de Síntomasdel Catéter Ureteral (USSQ) y la la escala visualanáloga (EVA) de 10 cm. Se compararon las puntuaciones medias de los dominios del USSQ y las puntuacionesmedias de la EVA. RESULTADOS: Se incluyeron y evaluaron 149 pacientes.La edad media fue de 48,2±15,1 años. No seencontraron diferencias significativas en las puntuacionesmedias de cada dominio principal en la USSQo la EVA. La presencia de dolor en el flanco durante lamicción estuvo presente en el 73,5% y el 52,5% parael grupo de hidronefrosis baja vs. moderada respectivamente(p=0,01). El subanálisis por género fue 78,7% vs 44,0 % (p=0,00) y 58,6 % vs 66,6 % (p=0,6) delgrupo de baja y moderada en hombres y mujeres respectivamente.El análisis de la puntuación de los ítems de laUSSQ reveló que el grupo de hidronefrosis moderadapresentó menos "dolor o molestia al orinar", menos"presencia de dolor de espalda al orinar", menos "admisióno procedimiento por molestia" y menos "sensaciónde reinserción". CONCLUSIÓN: Los pacientes del grupo de hidronefrosismoderada no ofrecen ventajas significativas encuanto a los síntomas de evacuación, el dolor, la saludgeneral, las cuestiones sexuales o los problemasdeterminados por el USSQ o en EVA. Sin embargo, elsubanálisis informó de ventajas relativas al dolor ypreguntas adicionales. Los hombres con hidronefrosismoderada presentaban un dolor estadísticamente significativodurante la micción.

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.

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.

Antegrade Ejaculation Preservation Technique with GreenLight XPS 180-W: Functional Ejaculatory Results.

Introduction: Ejaculatory dysfunction is a common complication of surgeries for benign prostatic obstruction. It causes a clear deterioration in quality of life. Techniques have been developed to attempt to preserve antegrade ejaculation (AE). Our objective was to analyze results of ejaculatory function using an AE preservation technique during anatomical vaporization with XPS 180-W. Methods: Between 2017 and 2019, sexually active patients were treated using this technique by the same surgical team. A questionnaire (MSHQ-EjD Short Form) was mailed, patients who did not answer were contacted by phone or personally during follow-up. Responses were analyzed. Voiding function was evaluated using International Prostatic Symptoms Score (IPSS), Qmax, and postvoid residual volume. t-Test for paired samples was used to compare conformity of patients with and without AE and voiding results. A p < 0.05 was considered statistically significant. Results: In total, 77 of 112 patients (68.8%) completed questionnaires and were included. Mean age was 64.1 years (standard deviation [SD] 6.9) and median prostate size was 57.2 g (interquartilic range 30-85). A total of 68 of 77 (88.3%) patients reported AE. Of these, 58 (85.3%) reported AE always or most of the time and 10 (14.7%) reported AE half of the time. In total, 42 (61.7%) patients had preserved strength or slightly less than before the procedure, and 33 (48.5%) reported the same or slightly less volume than before. In terms of satisfaction, the average response values of patients with preserved AE and ejaculatory disfunction were 0.97 (SD 1.12) and 2.7 (SD 1.78), respectively (p = 0.000). Pre- and postoperative variables were as follows: mean Qmax was 11.6 mL/sec vs 19.6 (p = 0.00), mean IPSS was 13.8 vs 8.9 (p = 0.000), and mean postvoiding residual urine was 125.3 vs 33.1 mL (p = 0.00), respectively. Conclusion: It is feasible to perform the AE preservation technique with anatomical vaporization XPS 180-W. In our medium size prostate series, we had a satisfactory patient perception of the ejaculatory function and satisfactory voiding function results.

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.

[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.

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.

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.

Nephron-sparing surgery: our experience in open and laparoscopic approach in 254 cases.

OBJECTIVES: The majority of renal cell carcinomas are now incidentally detected as small renal masses in asymptomatic patients due to the widespread use of ultrasound and new improved noninvasive abdominal imaging modalities. Nephron-sparing surgery is the treatment of choice for patients with small renal masses in presence of normal contralateral kidney or in presence of an anatomic or functional solitary kidney. We reviewed retrospectively our experience in open and laparoscopic partial nephrectomy. METHODS: The records for all patients who underwent nephron-sparing surgery for a renal mass since 1995 at British Hospital of Buenos Aires and Hospital Aleman and since 2000 at Hospital Universitario Austral were reviewed. The most relevant data of 246 patients were collected, with special focus on demographic data, operative details, pathology results, complications and outcome in cancer control. RESULTS: We have performed 254 nephron-sparing surgeries. Open partial nephrectomy was performed in 220 procedures and the laparoscopic partial nephrectomy since 2001 in 34 patients. The indication was elective or relative in 236 patients with 8 patients with bilateral tumors and 18 tumors in a solitary kidney. The pedicle was clamped in 168 procedures with hypothermia in 43 patients. Mean ischemia time was 24.7 minutes. Average tumor size was 3.49 cm. The pathologic findings demonstrate a carcinoma in 193 cases and benign lesions in 61 patients (24%). One patient presented a positive surgical margin in the pathologic examination, but subsequent nephrectomy was negative for residual tumor. One patient presented a pseudo-tumoral mass on follow-up on CT scan and MRI, but nephrectomy was negative for residual tumor. There were postoperative complications in 20 patients (7.9 %). Oncologic follow up was available in 84% of the patients for an average of 46.6 months showing progression with metastasis in 8 patients. Local recurrence was observed in 4 patients (2%). One patient developed a tumor in the contralateral kidney 20 months after partial nephrectomy and another one 10 years later. The cancer specific survival and overall survival rates were 98 % and 95% respectively. In the last year the laparoscopic approach duplicated the indications of all previous years. CONCLUSIONS: Open partial nephrectomy is considered nowadays the gold standard treatment of small renal masses, and in our experience it is a safe and effective technique of treatment of these tumors. The evolution of the technology and the acquirement of laparoscopic skills allow us in selected cases to duplicate the open approach in a laparoscopic way, obtaining similar results.

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.